Helicases are enzymes that use ATP-driven motor force to unwind double-stranded DNA or RNA. Recently, increasing evidence demonstrates that some helicases also possess rewinding activity—in other words, they can anneal two complementary single-stranded nucleic acids. All five members of the human RecQ helicase family, helicase PIF1, mitochondrial helicase TWINKLE, and helicase/nuclease Dna2 have been shown to possess strand-annealing activity. Moreover, two recently identified helicases—HARP and AH2 have only ATP-dependent rewinding activity. These findings not only enhance our understanding of helicase enzymes but also establish the presence of a new type of protein: annealing helicases. This paper discusses what is known about these helicases, focusing on their biochemical activity to zip and unzip double-stranded DNA and/or RNA, their possible regulation mechanisms, and biological functions. 1. Introduction Helicases are molecular motors that couple the energy of nucleoside triphosphate hydrolysis to the unwinding and remodeling of structured DNA or RNA [1–3]. The number of helicases expressed in higher organisms is strikingly high, with approximately 1% of the genes in many eukaryotic genomes apparently encoding RNA or DNA helicases. Helicases are involved in virtually all aspects of nucleic acid metabolism, including replication, repair, recombination, transcription, chromosome segregation, and telomere maintenance [4–7]. Based on their substrates, helicases can be classified as DNA or RNA helicases, although some can function on both DNA and RNA molecules [8]. DNA helicases have been reported to function in a variety of DNA metabolic processes, including unwinding duplex or alternative DNA structures (triplex, G-quadruplex), stripping protein bound to DNA, and chromatin remodeling [5, 6, 9, 10]. Traditionally, helicases are known to unwind double-stranded DNA or RNA in an ATP-dependent manner. However, increasing evidence suggests that some helicases can rewind, or anneal, complementary strands of polynucleic acids in the presence or absence of nucleoside triphosphate (Figure 1). Moreover, two so-called human helicases that were identified recently appear to only have ATP-dependent rewinding activity [11–15]. These discoveries not only enrich the definition of helicases but also establish the presence of a new type of protein: annealing helicase. The mechanism of this novel strand annealing activity and its biological consequences remain largely unknown. In this paper, I will provide a brief overview of strand annealing activity found in various
References
[1]
T. M. Lohman and K. P. Bjornson, “Mechanisms of helicase-catalyzed DNA unwinding,” Annual Review of Biochemistry, vol. 65, pp. 169–214, 1996.
[2]
M. R. Singleton, M. S. Dillingham, and D. B. Wigley, “Structure and mechanism of helicases and nucleic acid translocases,” Annual Review of Biochemistry, vol. 76, pp. 23–50, 2007.
[3]
S. S. Patel and I. Donmez, “Mechanisms of helicases,” Journal of Biological Chemistry, vol. 281, no. 27, pp. 18265–18268, 2006.
[4]
R. M. Brosh Jr. and V. A. Bohr, “Human premature aging, DNA repair and RecQ helicases,” Nucleic Acids Research, vol. 35, no. 22, pp. 7527–7544, 2007.
[5]
M. S. Dillingham, “Superfamily I helicases as modular components of DNA-processing machines,” Biochemical Society Transactions, vol. 39, no. 2, pp. 413–423, 2011.
[6]
K. A. Bernstein, S. Gangloff, and R. Rothstein, “The RecQ DNA helicases in DNA repair,” Annual Review of Genetics, vol. 44, pp. 393–417, 2010.
[7]
E. Jankowsky, “RNA helicases at work: binding and rearranging,” Trends in Biochemical Sciences, vol. 36, no. 1, pp. 19–29, 2011.
[8]
A. M. Pyle, “Translocation and unwinding mechanisms of RNA and DNA helicases,” Annual Review of Biophysics, vol. 37, pp. 317–336, 2008.
[9]
D. K. Singh, A. K. Ghosh, D. L. Croteau, and V. A. Bohr, “RecQ helicases in DNA double strand break repair and telomere maintenance,” Mutation Research. In press.
[10]
Y. Wu, A. N. Suhasini, and R. M. Brosh Jr., “Welcome the family of FANCJ-like helicases to the block of genome stability maintenance proteins,” Cellular and Molecular Life Sciences, vol. 66, no. 7, pp. 1209–1222, 2009.
[11]
C. E. Bansbach, R. Bétous, C. A. Lovejoy, G. G. Glick, and D. Cortez, “The annealing helicase SMARCAL1 maintains genome integrity at stalled replication forks,” Genes and Development, vol. 23, no. 20, pp. 2405–2414, 2009.
[12]
A. Ciccia, A. L. Bredemeyer, M. E. Sowa et al., “The SIOD disorder protein SMARCAL1 is an RPA-interacting protein involved in replication fork restart,” Genes and Development, vol. 23, no. 20, pp. 2415–2425, 2009.
[13]
J. Yuan, G. Ghosal, and J. Chen, “The annealing helicase HARP protects stalled replication forks,” Genes and Development, vol. 23, no. 20, pp. 2394–2399, 2009.
[14]
T. Yusufzai and J. T. Kadonaga, “HARP is an ATP-driven annealing helicase,” Science, vol. 322, no. 5902, pp. 748–750, 2008.
[15]
T. Yusufzai and J. T. Kadonaga, “Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 49, pp. 20970–20973, 2010.
[16]
G. M. Weinstock, K. McEntee, and I. R. Lehman, “ATP-dependent renaturation of DNA catalyzed by the recA protein of Escherichia coli,” Proceedings of the National Academy of Sciences of the United States of America, vol. 76, no. 1, pp. 126–130, 1979.
[17]
S. L. Keener and K. Mcentee, “Homologous pairing of single-stranded circular DNAs catalyzed by recA protein,” Nucleic Acids Research, vol. 12, no. 15, pp. 6127–6139, 1984.
[18]
B. Muller and A. Stasiak, “RecA-mediated annealing of single-stranded DNA and its relation to the mechanism of homologous recombination,” Journal of Molecular Biology, vol. 221, no. 1, pp. 131–145, 1991.
[19]
D. P. Kirkpatrick, B. J. Rao, and C. M. Radding, “RNA-DNA hybridization promoted by E.Coli RecA protein,” Nucleic Acids Research, vol. 20, no. 16, pp. 4339–4346, 1992.
[20]
M. E. Cusick and M. Belfort, “Domain structure and RNA annealing activity of the Escherichia coli regulatory protein StpA,” Molecular Microbiology, vol. 28, no. 4, pp. 847–857, 1998.
[21]
N. Kantake, M. V. V. M. Madiraju, T. Sugiyama, and S. C. Kowalczykowski, “Escherichia coli RecO protein anneals ssDNA complexed with its cognate ssDNA-binding protein: a common step in genetic recombination,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 24, pp. 15327–15332, 2002.
[22]
Z. Zuo, H. K. Lin, and M. A. Trakselis, “Strand annealing and terminal transferase activities of a B-family DNA polymerase,” Biochemistry, vol. 50, no. 23, pp. 5379–5390, 2011.
[23]
U. H. Mortensen, C. Bendixen, I. Sunjevaric, and R. Rothstein, “DNA strand annealing is promoted by the yeast RaD52 protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 20, pp. 10729–10734, 1996.
[24]
Y. Wu, N. Kantake, T. Sugiyama, and S. C. Kowalczykowski, “Rad51 protein controls Rad52-mediated DNA annealing,” Journal of Biological Chemistry, vol. 283, no. 21, pp. 14883–14892, 2008.
[25]
Y. Wu, T. Sugiyama, and S. C. Kowalczykowski, “DNA annealing mediated by Rad52 and Rad59 proteins,” Journal of Biological Chemistry, vol. 281, no. 22, pp. 15441–15449, 2006.
[26]
T. Sugiyama, J. H. New, and S. C. Kowalczykowski, “DNA annealing by Rad52 protein is stimulated by specific interaction with the complex of replication protein A and single-stranded DNA,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 11, pp. 6049–6054, 1998.
[27]
N. Sugawara, G. Ira, and J. E. Haber, “DNA length dependence of the single-strand annealing pathway and the role of Saccharomyces cerevisiae RAD59 in double-strand break repair,” Molecular and Cellular Biology, vol. 20, no. 14, pp. 5300–5309, 2000.
[28]
A. P. Davis and L. S. Symington, “The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing,” Genetics, vol. 159, no. 2, pp. 515–525, 2001.
[29]
E. Hitti, A. Neunteufl, and M. F. Jantsch, “The double-stranded RNA-binding protein Xlrbpa promotes RNA strand annealing,” Nucleic Acids Research, vol. 26, no. 19, pp. 4382–4388, 1998.
[30]
M. Kuciak, C. Gabus, R. Ivanyi-Nagy et al., “The HIV-1 transcriptional activator Tat has potent nucleic acid chaperoning activities in vitro,” Nucleic Acids Research, vol. 36, no. 10, pp. 3389–3400, 2008.
[31]
C. Boudier, R. Storchak, K. K. Sharma et al., “The mechanism of HIV-1 Tat-directed nucleic acid annealing supports its role in reverse transcription,” Journal of Molecular Biology, vol. 400, no. 3, pp. 487–501, 2010.
[32]
W. L. Pong, Z. S. Huang, P. G. Teoh, C. C. Wang, and H. N. Wu, “RNA binding property and RNA chaperone activity of dengue virus core protein and other viral RNA-interacting proteins,” FEBS Letters, vol. 585, pp. 2575–2581, 2011.
[33]
A. Kumar and S. H. Wilson, “Studies of the strand-annealing activity of mammalian hnRNP complex protein A1,” Biochemistry, vol. 29, no. 48, pp. 10717–10722, 1990.
[34]
F. Cobianchi, C. Calvio, M. Stoppini, M. Buvoli, and S. Riva, “Phosphorylation of human hnRNP protein A1 abrogates in vitro strand annealing activity,” Nucleic Acids Research, vol. 21, no. 4, pp. 949–955, 1993.
[35]
H. Idriss, A. Kumar, J. R. Casas-Finet, H. Guo, Z. Damuni, and S. H. Wilson, “Regulation of in vitro nucleic acid strand annealing activity of heterogeneous nuclear ribonucleoprotein protein A1 by reversible phosphorylation,” Biochemistry, vol. 33, no. 37, pp. 11382–11390, 1994.
[36]
H. W. Sturzbecher, R. Brain, T. Maimets, C. Addison, K. Rudge, and J. R. Jenkins, “Mouse p53 blocks SV40 DNA replication in vitro and downregulates T antigen DNA helicase activity,” Oncogene, vol. 3, no. 4, pp. 405–413, 1988.
[37]
P. Oberosler, P. Hloch, U. Ramsperger, and H. Stahl, “p53-catalyzed annealing of complementary single-stranded nucleic acids,” EMBO Journal, vol. 12, no. 6, pp. 2389–2396, 1993.
[38]
M. de Jager, M. L. G. Dronkert, M. Modesti, C. E. M. T. Beerens, R. Kanaar, and D. C. van Gent, “DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair pathways,” Nucleic Acids Research, vol. 29, no. 6, pp. 1317–1325, 2001.
[39]
H. Yokoyama, N. Sarai, W. Kagawa et al., “Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex,” Nucleic Acids Research, vol. 32, no. 8, pp. 2556–2565, 2004.
[40]
B. C. Valdez, D. Henning, K. Perumal, and H. Busch, “RNA-unwinding and RNA-folding activities of RNA helicase II/Gu—two activities in separate domains of the same protein,” European Journal of Biochemistry, vol. 250, no. 3, pp. 800–807, 1997.
[41]
O. G. R？ssler, A. Straka, and H. Stahl, “Rearrangement of structured RNA via branch migration structures catalysed by the highly related DEAD-box proteins p68 and p72,” Nucleic Acids Research, vol. 29, no. 10, pp. 2088–2096, 2001.
[42]
H. Uhlmann-Schiffler, C. Jalal, and H. Stahl, “Ddx42p—a human DEAD box protein with RNA chaperone activities,” Nucleic Acids Research, vol. 34, no. 1, pp. 10–22, 2006.
[43]
S. Zhang and F. Grosse, “Multiple functions of nuclear DNA Helicase II (RNA helicase A) in nucleic acid metabolism,” Acta Biochimica et Biophysica Sinica, vol. 36, no. 3, pp. 177–183, 2004.
[44]
L. Xing, C. Liang, and L. Kleiman, “Coordinate roles of gag and RNA helicase A in promoting the annealing of tRNA3Lysto HIV-1 RNA,” Journal of Virology, vol. 85, no. 4, pp. 1847–1860, 2011.
[45]
Q. Yang and E. Jankowsky, “ATP- and ADP-dependent modulation of RNA unwinding and strand annealing activities by the DEAD-box protein DED1,” Biochemistry, vol. 44, no. 41, pp. 13591–13601, 2005.
[46]
C. Halls, S. Mohr, M. del Campo, Q. Yang, E. Jankowsky, and A. M. Lambowitz, “Involvement of DEAD-box proteins in group I and group II intron splicing. Biochemical characterization of Mss116p, ATP hydrolysis-dependent and -independent mechanisms, and general RNA chaperone activity,” Journal of Molecular Biology, vol. 365, no. 3, pp. 835–855, 2007.
[47]
B. Chamot, K. R. Colvin, S. L. Kujat-Choy, and G. W. Owttrim, “RNA structural rearrangement via unwinding and annealing by the cyanobacterial RNA helicase, CrhR,” Journal of Biological Chemistry, vol. 280, no. 3, pp. 2036–2044, 2005.
[48]
L. G. Gebhard, S. B. Kaufman, and A. V. Gamarnik, “Novel ATP-independent RNA annealing activity of the dengue virus NS3 helicase,” PLoS One, vol. 7, no. 4, article e36244, 2012.
[49]
S. Sharma, J. A. Sommers, S. Choudhary et al., “Biochemical analysis of the DNA unwinding and strand annealing activities catalyzed by human RECQ1,” Journal of Biological Chemistry, vol. 280, no. 30, pp. 28072–28084, 2005.
[50]
L. Muzzolini, F. Beuron, A. Patwardhan et al., “Different quaternary structures of human RECQ1 are associated with its dual enzymatic activity,” PLoS Biology, vol. 5, no. 2, article e20, 2007.
[51]
A. Machwe, L. Xiao, J. Groden, S. W. Matson, and D. K. Orren, “RecQ family members combine strand pairing and unwinding activities to catalyze strand exchange,” Journal of Biological Chemistry, vol. 280, no. 24, pp. 23397–23407, 2005.
[52]
M. Muftuoglu, T. Kulikowicz, G. Beck, J. W. Lee, J. Piotrowski, and V. A. Bohr, “Intrinsic ssDNA annealing activity in the C-terminal region of WRN,” Biochemistry, vol. 47, no. 39, pp. 10247–10254, 2008.
[53]
C. F. Cheok, L. Wu, P. L. Garcia, P. Janscak, and I. D. Hickson, “The Bloom's syndrome helicase promotes the annealing of complementary single-stranded DNA,” Nucleic Acids Research, vol. 33, no. 12, pp. 3932–3941, 2005.
[54]
X. Xu and Y. Liu, “Dual DNA unwinding activities of the Rothmund-Thomson syndrome protein, RECQ4,” EMBO Journal, vol. 28, no. 5, pp. 568–577, 2009.
[55]
P. L. Garcia, Y. Liu, J. Jiricny, S. C. West, and P. Janscak, “Human RECQ51β, a protein with DNA helicase and strand-annealing activities in a single polypeptide,” EMBO Journal, vol. 23, no. 14, pp. 2882–2891, 2004.
[56]
Y. Gu, Y. Masuda, and K. Kamiya, “Biochemical analysis of human PIF1 helicase and functions of its N-terminal domain,” Nucleic Acids Research, vol. 36, no. 19, pp. 6295–6308, 2008.
[57]
T. Masuda-Sasa, P. Polaczek, and J. L. Campbell, “Single strand annealing and ATP-independent strand exchange activities of yeast and human DNA2: possible role in okazaki fragment maturation,” Journal of Biological Chemistry, vol. 281, no. 50, pp. 38555–38564, 2006.
[58]
M. Muftuoglu, S. Sharma, T. Thorslund et al., “Cockayne syndrome group B protein has novel strand annealing and exchange activities,” Nucleic Acids Research, vol. 34, no. 1, pp. 295–304, 2006.
[59]
D. Sen, D. Nandakumar, G. Q. Tang, and S. S. Patel, “The Human Mitochondrial DNA helicase TWINKLE is both an unwinding and an annealing helicase,” The Journal of Biological Chemistry, vol. 287, pp. 14545–14556, 2012.
[60]
Y. Hu, X. Lu, E. Barnes, M. Yan, H. Lou, and G. Luo, “Recql5 and Blm RecQ DNA helicases have nonredundant roles in suppressing crossovers,” Molecular and Cellular Biology, vol. 25, no. 9, pp. 3431–3442, 2005.
[61]
Y. Hu, S. Raynard, M. G. Sehorn et al., “RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments,” Genes and Development, vol. 21, no. 23, pp. 3073–3084, 2007.
[62]
D. Li, H. Liu, L. Jiao et al., “Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival,” Cancer Research, vol. 66, no. 6, pp. 3323–3330, 2006.
[63]
D. Li, M. Frazier, D. B. Evans et al., “Single nucleotide polymorphisms of RecQ1, RAD54L, and ATM genes are associated with reduced survival of pancreatic cancer,” Journal of Clinical Oncology, vol. 24, no. 11, pp. 1720–1728, 2006.
[64]
C. F. Chen and S. J. Brill, “An essential DNA strand-exchange activity is conserved in the divergent N-termini of BLM orthologs,” EMBO Journal, vol. 29, no. 10, pp. 1713–1725, 2010.
[65]
B. T. Weinert and D. C. Rio, “DNA strand displacement, strand annealing and strand swapping by the Drosophila Bloom's syndrome helicase,” Nucleic Acids Research, vol. 35, no. 4, pp. 1367–1376, 2007.
[66]
T. George, Q. Wen, R. Griffiths, A. Ganesh, M. Meuth, and C. M. Sanders, “Human Pif1 helicase unwinds synthetic DNA structures resembling stalled DNA replication forks,” Nucleic Acids Research, vol. 37, no. 19, pp. 6491–6502, 2009.
[67]
J. Yin, Y. T. Kwon, A. Varshavsky, and W. Wang, “RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway,” Human Molecular Genetics, vol. 13, no. 20, pp. 2421–2430, 2004.
[68]
M. A. Macris, L. Krejci, W. Bussen, A. Shimamoto, and P. Sung, “Biochemical characterization of the RECQ4 protein, mutated in Rothmund-Thomson syndrome,” DNA Repair, vol. 5, no. 2, pp. 172–180, 2006.
[69]
T. Suzuki, T. Kohno, and Y. Ishimi, “DNA helicase activity in purified human RECQL4 protein,” Journal of Biochemistry, vol. 146, no. 3, pp. 327–335, 2009.
[70]
M. L. Rossi, A. K. Ghosh, T. Kulikowicz, D. L. Croteau, and V. A. Bohr, “Conserved helicase domain of human RecQ4 is required for strand annealing-independent DNA unwinding,” DNA Repair, vol. 9, no. 7, pp. 796–804, 2010.
[71]
M. L. Bochman, N. Sabouri, and V. A. Zakian, “Unwinding the functions of the Pif1 family helicases,” DNA Repair, vol. 9, no. 3, pp. 237–249, 2010.
[72]
Y. H. Kang, C. H. Lee, and Y. S. Seo, “Dna2 on the road to Okazaki fragment processing and genome stability in eukaryotes,” Critical Reviews in Biochemistry and Molecular Biology, vol. 45, no. 2, pp. 71–96, 2010.
[73]
V. Natale, “A comprehensive description of the severity groups in Cockayne syndrome,” American Journal of Medical Genetics A, vol. 155, no. 5, pp. 1081–1095, 2011.
[74]
S. W. Nelson and S. J. Benkovic, “The T4 phage UvsW protein contains both DNA unwinding and strand annealing activities,” Journal of Biological Chemistry, vol. 282, no. 1, pp. 407–416, 2007.
[75]
Z. Li, S. Lu, G. Hou et al., “Hjm/Hel308a DNA Helicase from Sulfolobus tokodaii promotes replication fork regression and interacts with Hjc endonuclease in vitro,” Journal of Bacteriology, vol. 190, no. 8, pp. 3006–3017, 2008.
[76]
M. de Felice, V. Aria, L. Esposito et al., “A novel DNA helicase with strand-annealing activity from the crenarchaeon sulfolobus solfataricus,” Biochemical Journal, vol. 408, no. 1, pp. 87–95, 2007.
[77]
S. V. Balasingham, E. D. Zegeye, H. Homberset et al., “Enzymatic activities and DNA substrate specificity of mycobacterium tuberculosis DNA helicase XPB,” PLoS One, vol. 7, article e36960, 2012.
[78]
C. F. Boerkoel, H. Takashima, J. John et al., “Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia,” Nature Genetics, vol. 30, no. 2, pp. 215–220, 2002.
[79]
L. I. Elizonod, K. S. Cho, W. Zhang et al., “Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation,” Journal of Medical Genetics, vol. 46, no. 1, pp. 49–59, 2009.
[80]
T. Yusufzai, X. Kong, K. Yokomori, and J. T. Kadonaga, “The annealing helicase HARP is recruited to DNA repair sites via an interaction with RPA,” Genes and Development, vol. 23, no. 20, pp. 2400–2404, 2009.
[81]
L. Postow, E. M. Woo, B. T. Chait, and H. Funabiki, “Identification of SMARCAL1 as a component of the DNA damage response,” Journal of Biological Chemistry, vol. 284, no. 51, pp. 35951–35961, 2009.
[82]
G. Ghosal, J. Yuan, and J. Chen, “The HARP domain dictates the annealing helicase activity of HARP/SMARCAL1,” EMBO Reports, vol. 12, no. 6, pp. 574–580, 2011.
[83]
R. Betous, A. C. Mason, R. P. Rambo et al., “SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication,” Genes & Development., vol. 26, pp. 151–162, 2012.
[84]
A. Flaus, D. M. A. Martin, G. J. Barton, and T. Owen-Hughes, “Identification of multiple distinct Snf2 subfamilies with conserved structural motifs,” Nucleic Acids Research, vol. 34, no. 10, pp. 2887–2905, 2006.
[85]
B. L. Stoddard, “Homing endonuclease structure and function,” Quarterly Reviews of Biophysics, vol. 38, no. 1, pp. 49–95, 2005.
[86]
R. B. Guo, P. Rigolet, H. Ren et al., “Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein,” Nucleic Acids Research, vol. 35, no. 18, pp. 6297–6310, 2007.
[87]
M. E. Fairman-Williams, U. P. Guenther, and E. Jankowsky, “SF1 and SF2 helicases: family matters,” Current Opinion in Structural Biology, vol. 20, no. 3, pp. 313–324, 2010.
[88]
B. Lucic, Y. Zhang, O. King et al., “A prominent β-hairpin structure in the winged-helix domain of RECQ1 is required for DNA unwinding and oligomer formation,” Nucleic Acids Research, vol. 39, no. 5, pp. 1703–1717, 2011.
[89]
J. L. Howard, S. Delmas, I. Ivancic-Bace, and E. L. Bolt, “Helicase dissociation and annealing of RNA-DNA hybrids by escherichia coli Cas3 protein,” Biochemical Journal, vol. 439, pp. 85–95, 2011.
[90]
E. Fanning, V. Klimovich, and A. R. Nager, “A dynamic model for replication protein A (RPA) function in DNA processing pathways,” Nucleic Acids Research, vol. 34, no. 15, pp. 4126–4137, 2006.
[91]
M. S. Wold, “Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism,” Annual Review of Biochemistry, vol. 66, pp. 61–92, 1997.
[92]
R. M. Brosh Jr., D. K. Orren, J. O. Nehlin et al., “Functional and physical interaction between WRN helicase and human replication protein A,” Journal of Biological Chemistry, vol. 274, no. 26, pp. 18341–18350, 1999.
[93]
J. C. Shen, M. D. Gray, J. Oshima, and L. A. Loeb, “Characterization of Werner syndrome protein DNA helicase activity: directionality, substrate dependence and stimulation by replication protein A,” Nucleic Acids Research, vol. 26, no. 12, pp. 2879–2885, 1998.
[94]
R. M. Brosh Jr., J. L. Li, M. K. Kenny et al., “Replication protein a physically interacts with the Bloom's syndrome protein and stimulates its helicase activity,” Journal of Biological Chemistry, vol. 275, no. 31, pp. 23500–23508, 2000.
[95]
S. Cui, D. Arosio, K. M. Doherty, R. M. Brosh Jr., A. Falaschi, and A. Vindigni, “Analysis of the unwinding activity of the dimeric RECQ1 helicase in the presence of human replication protein A,” Nucleic Acids Research, vol. 32, no. 7, pp. 2158–2170, 2004.
[96]
R. Gupta, S. Sharma, J. A. Sommers, M. K. Kenny, S. B. Cantor, and R. M. Brosh Jr., “FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein a and interacts physically and functionally with the single-stranded DNA-binding protein,” Blood, vol. 110, no. 7, pp. 2390–2398, 2007.
[97]
H. Yan, T. Toczylowski, J. McCane, C. Chen, and S. Liao, “Replication protein A promotes 5′→3′ end processing during homology-dependent DNA double-strand break repair,” Journal of Cell Biology, vol. 192, no. 2, pp. 251–261, 2011.
[98]
C. G. Lee, P. D. Zamore, M. R. Green, and J. Hurwitz, “RNA annealing activity is intrinsically associated with U2AF,” Journal of Biological Chemistry, vol. 268, no. 18, pp. 13472–13478, 1993.
[99]
K. S. Trego, S. B. Chernikova, A. R. Davalos et al., “The DNA repair endonuclease XPG interacts directly and functionally with the WRN helicase defective in Werner syndrome,” Cell Cycle, vol. 10, no. 12, pp. 1998–2007, 2011.
[100]
S. Sharma and R. M. Brosh Jr., “Human RECQ1 is a DNA damage responsive protein required for genotoxic stress resistance and suppression of sister chromatid exchanges,” PLoS ONE, vol. 2, no. 12, article e1297, 2007.
[101]
M. Ababou, S. Dutertre, Y. Lécluse, R. Onclercq, B. Chatton, and M. Amor-Guéret, “ATM-dependent phosphorylation and accumulation of endogenous BLM protein in response to ionizing radiation,” Oncogene, vol. 19, no. 52, pp. 5955–5963, 2000.
[102]
H. Beamish, P. Kedar, H. Kaneko et al., “Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM,” Journal of Biological Chemistry, vol. 277, no. 34, pp. 30515–30523, 2002.
[103]
S. L. Davies, P. S. North, A. Dart, N. D. Lakin, and I. D. Hickson, “Phosphorylation of the bloom's syndrome helicase and its role in recovery from S-phase arrest,” Molecular and Cellular Biology, vol. 24, no. 3, pp. 1279–1291, 2004.
[104]
S. Sengupta, A. I. Robles, S. P. Linke et al., “Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest,” Journal of Cell Biology, vol. 166, no. 6, pp. 801–813, 2004.
[105]
E. Bayart, S. Dutertre, C. Jaulin, R. B. Guo, G. X. Xu, and M. Amor-Guéret, “The bloom syndrome helicase is a substrate of the mitotic Cdc2 kinase,” Cell Cycle, vol. 5, no. 15, pp. 1681–1686, 2006.
[106]
M. Leng, D. W. Chan, H. Luo, C. Zhu, J. Qin, and Y. Wang, “MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 31, pp. 11485–11490, 2006.
[107]
P. Pichierri, F. Rosselli, and A. Franchitto, “Werner's syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replication arrest and DNA damage induced during the S phase of the cell cycle,” Oncogene, vol. 22, no. 10, pp. 1491–1500, 2003.
[108]
F. Ammazzalorso, L. M. Pirzio, M. Bignami, A. Franchitto, and P. Pichierri, “ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks and promote replication fork recovery,” EMBO Journal, vol. 29, no. 18, pp. 3156–3169, 2010.
[109]
S. Eladad, T. Z. Ye, P. Hu et al., “Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification,” Human Molecular Genetics, vol. 14, no. 10, pp. 1351–1365, 2005.
[110]
G. Blandert, N. Zalle, Y. Daniely, J. Taplick, M. D. Gray, and M. Oren, “DNA damage-induced translocation of the werner helicase is regulated by acetylation,” Journal of Biological Chemistry, vol. 277, no. 52, pp. 50934–50940, 2002.
[111]
J. M. Clewing, H. Fryssira, D. Goodman et al., “Schimke immunoosseous dysplasia: suggestions of genetic diversity,” Human Mutation, vol. 28, no. 3, pp. 273–283, 2007.
[112]
R. Driscoll and K. A. Cimprich, “HARPing on about the DNA damage response during replication,” Genes and Development, vol. 23, no. 20, pp. 2359–2365, 2009.
[113]
L. Wu and I. D. Hickson, “DNA helicases required for homologous recombination and repair of damaged replication forks,” Annual Review of Genetics, vol. 40, pp. 279–306, 2006.
[114]
K. K. Dhillon, J. Sidorova, Y. Saintigny et al., “Functional role of the Werner syndrome RecQ helicase in human fibroblasts,” Aging Cell, vol. 6, no. 1, pp. 53–61, 2007.
[115]
M. Poot, J. S. Yom, S. H. Whang, J. T. Kato, K. A. Gollahon, and P. S. Rabinovitch, “Werner syndrome cells are sensitive to DNA cross-linking drugs,” The FASEB Journal, vol. 15, no. 7, pp. 1224–1226, 2001.
[116]
G. J. Hook, E. Kwok, and J. A. Heddle, “Sensitivity of Bloom syndrome fibroblasts to mitomycin C,” Mutation Research, vol. 131, no. 5-6, pp. 223–230, 1984.
[117]
W. Jin, H. Liu, Y. Zhang, S. K. Otta, S. E. Plon, and L. L. Wang, “Sensitivity of RECQL4-deficient fibroblasts from Rothmund-Thomson syndrome patients to genotoxic agents,” Human Genetics, vol. 123, no. 6, pp. 643–653, 2008.
[118]
R. Mendoza-Maldonado, V. Faoro, S. Bajpai et al., “The human RECQ1 helicase is highly expressed in glioblastoma and plays an important role in tumor cell proliferation,” Molecular Cancer, vol. 10, article 83, 2011.
[119]
Y. Hu, X. Lu, G. Zhou, E. L. Barnes, and G. Luo, “Recql5 plays an important role in DNA replication and cell survival after camptothecin treatment,” Molecular Biology of the Cell, vol. 20, no. 1, pp. 114–123, 2009.
[120]
A. Constantinou, M. Tarsounas, J. K. Karow et al., “Werner's syndrome protein (WRN) migrates Holliday junctions and co-localizes with RPA upon replication arrest,” EMBO Reports, vol. 1, no. 1, pp. 80–84, 2000.
[121]
J. K. Karow, A. Constantinou, J. L. Li, S. C. West, and I. D. Hickson, “The Bloom's syndrome gene product promotes branch migration of Holliday junctions,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 12, pp. 6504–6508, 2000.
[122]
A. Machwe, R. Karale, X. Xu, Y. Liu, and D. K. Orren, “The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks,” Biochemistry, vol. 50, pp. 6774–6788, 2011.
[123]
T. Weitao, M. Budd, L. L. M. Hoopes, and J. L. Campbell, “Dna2 helicase/nuclease causes replicative fork stalling and double-strand breaks in the ribosomal DNA of saccharomyces cerevisiae,” Journal of Biological Chemistry, vol. 278, no. 25, pp. 22513–22522, 2003.
[124]
M. E. Budd and J. L. Campbell, “Interplay of Mre11 nuclease with Dna2 plus Sgs1 in Rad51-dependent recombinational repair,” PLoS ONE, vol. 4, no. 1, article e4267, 2009.
[125]
L. S. Symington and J. Gautier, “Double-strand break end resection and repair pathway choice,” Annual Review of Genetics, vol. 45, pp. 247–271, 2011.
[126]
R. Kanagaraj, N. Saydam, P. L. Garcia, L. Zheng, and P. Janscak, “Human RECQ5β helicase promotes strand exchange on synthetic DNA structures resembling a stalled replication fork,” Nucleic Acids Research, vol. 34, no. 18, pp. 5217–5231, 2006.
[127]
M. McVey and S. E. Lee, “MMEJ repair of double-strand breaks (director's cut): deleted sequences and alternative endings,” Trends in Genetics, vol. 24, no. 11, pp. 529–538, 2008.
[128]
K. Kikuchi, H. I. Abdel-Aziz, Y. Taniguchi, M. Yamazoe, S. Takeda, and K. Hirota, “Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences,” Journal of Biological Chemistry, vol. 284, no. 39, pp. 26360–26367, 2009.
[129]
A. Mannuss, S. Dukowic-Schulze, S. Suer, F. Hartung, M. Pacher, and H. Puchta, “RAD5A, RECQ4A, AND MUS81 have specific functions in homologous recombination and define different pathways of dna repair in arabidopsis thaliana,” Plant Cell, vol. 22, no. 10, pp. 3318–3330, 2010.
[130]
E. Speina, L. Dawut, M. Hedayati et al., “Human RECQL5β stimulates flap endonuclease 1,” Nucleic Acids Research, vol. 38, no. 9, pp. 2904–2916, 2010.
[131]
W. Wang and R. A. Bambara, “Human bloom protein stimulates flap endonuclease 1 activity by resolving DNA secondary structure,” Journal of Biological Chemistry, vol. 280, no. 7, pp. 5391–5399, 2005.
[132]
R. M. Brosh Jr., C. Von Kobbe, J. A. Sommers et al., “Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity,” EMBO Journal, vol. 20, no. 20, pp. 5791–5801, 2001.
[133]
T. Sinkunas, G. Gasiunas, C. Fremaux, R. Barrangou, P. Horvath, and V. Siksnys, “Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system,” EMBO Journal, vol. 30, no. 7, pp. 1335–1342, 2011.
[134]
M. Fousteri, W. Vermeulen, A. A. van Zeeland, and L. H. F. Mullenders, “Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo,” Molecular Cell, vol. 23, no. 4, pp. 471–482, 2006.
[135]
M. Li, X. Xu, and Y. Liu, “The SET2-RPB1 interaction domain of human RECQ5 is important for transcription-associated genome stability,” Molecular and Cellular Biology, vol. 31, no. 10, pp. 2090–2099, 2011.
[136]
R. Kanagaraj, D. Huehn, A. MacKellar et al., “RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription,” Nucleic Acids Research, vol. 38, no. 22, pp. 8131–8140, 2010.
[137]
O. Aygün, X. Xu, Y. Liu et al., “Direct inhibition of RNA polymerase II transcription by RECQL5,” Journal of Biological Chemistry, vol. 284, no. 35, pp. 23197–23203, 2009.
[138]
O. Aygün, J. Svejstrup, and Y. Liu, “A RECQ5-RNA polymerase II association identified by targeted proteomic analysis of human chromatin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 25, pp. 8580–8584, 2008.
[139]
P. L. Opresko, M. Otterlei, J. Graakj？r et al., “The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2,” Molecular Cell, vol. 14, no. 6, pp. 763–774, 2004.
[140]
K. Lillard-Wetherell, A. Machwe, G. T. Langland et al., “Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2,” Human Molecular Genetics, vol. 13, no. 17, pp. 1919–1932, 2004.
[141]
A. K. Ghosh, M. L. Rossi, D. K. Singh et al., “RECQL4, the protein mutated in Rothmund-Thomson syndrome, functions in telomere maintenance,” Journal of Biological Chemistry, vol. 287, pp. 196–209, 2011.
[142]
K. Paeschke, K. R. McDonald, and V. A. Zakian, “Telomeres: structures in need of unwinding,” FEBS Letters, vol. 584, no. 17, pp. 3760–3772, 2010.
[143]
D. H. Zhang, B. Zhou, Y. Huang, L. X. Xu, and J. Q. Zhou, “The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity,” Nucleic Acids Research, vol. 34, no. 5, pp. 1393–1404, 2006.
[144]
T. Formosa and T. Nittis, “Dna2 mutants reveal interactions with Dna polymerase α and Ctf4, a Pol α accessory factor, and show that full Dna2 helicase activity is not essential for growth,” Genetics, vol. 151, no. 4, pp. 1459–1470, 1999.
[145]
J. Parenteau and R. J. Wellinger, “Accumulation of single-stranded DNA and destabilization of telomeric repeats in yeast mutant strains carrying a deletion of RAD27,” Molecular and Cellular Biology, vol. 19, no. 6, pp. 4143–4152, 1999.
[146]
G. Hauk and G. D. Bowman, “Structural insights into regulation and action of SWI2/SNF2 ATPases,” Current Opinion in Structural Biology, vol. 21, pp. 719–727, 2011.
[147]
P. McGlynn and R. G. Lloyd, “Action of RuvAB at replication fork structures,” Journal of Biological Chemistry, vol. 276, no. 45, pp. 41938–41944, 2001.
[148]
C. J. Rudolph, A. L. Upton, G. S. Briggs, and R. G. Lloyd, “Is RecG a general guardian of the bacterial genome?” DNA Repair, vol. 9, no. 3, pp. 210–223, 2010.
[149]
D. V. Bugreev, O. M. Mazina, and A. V. Mazin, “Rad54 protein promotes branch migration of Holliday junctions,” Nature, vol. 442, no. 7102, pp. 590–593, 2006.
[150]
E. C. Minca and D. Kowalski, “Multiple Rad5 activities mediate sister chromatid recombination to Bypass DNA damage at stalled replication forks,” Molecular Cell, vol. 38, no. 5, pp. 649–661, 2010.
[151]
A. Blastyák, L. Pintér, I. Unk, L. Prakash, S. Prakash, and L. Haracska, “Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression,” Molecular Cell, vol. 28, no. 1, pp. 167–175, 2007.
[152]
Y. J. Achar, D. Balogh, and L. Haracska, “Coordinated protein and DNA remodeling by human HLTF on stalled replication fork,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, pp. 14073–14078, 2011.
[153]
N. Janssen, J. E. Bergman, M. A. Swertz et al., “Mutation update on the CHD7 gene involved in CHARGE syndrome,” Human Mutation, vol. 33, no. 8, pp. 1149–1160, 2012.
[154]
K. Gari, C. Décaillet, A. Z. Stasiak, A. Stasiak, and A. Constantinou, “The fanconi anemia protein FANCM can promote branch migration of holliday junctions and replication forks,” Molecular Cell, vol. 29, no. 1, pp. 141–148, 2008.
[155]
K. Gari, C. Décaillet, M. Delannoy, L. Wu, and A. Constantinou, “Remodeling of DNA replication structures by the branch point translocase FANCM,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 42, pp. 16107–16112, 2008.
[156]
J. K. van Houdt, B. A. Nowakowska, S. B. Sousa, et al., “Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome,” Nature Genetics, vol. 44, supplement 1, pp. 445–449, 2012.
[157]
Y. Tsurusaki, N. Okamoto, H. Ohashi, et al., “Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome,” Nature Genetics, vol. 44, pp. 376–378, 2012.
