全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2013 

Etoposide Induces Nuclear Re-Localisation of AID

DOI: 10.1371/journal.pone.0082110

Full-Text   Cite this paper   Add to My Lib

Abstract:

During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the nucleus for 10 or more hours, during which time cells remain live and motile. Re-localisation is cell-cycle dependent and is only observed in G2. Analysis of DSB dynamics shows that AID is re-localised in response to etoposide treatment, however re-localisation occurs substantially after DSB formation and the levels of re-localisation do not correlate with γH2AX levels. We conclude that DSB formation initiates a slow-acting pathway which allows stable long-term nuclear localisation of AID, and that such a pathway may enable AID-induced DNA demethylation during epigenetic reprogramming.

References

[1]  Peled JU, Kuang FL, Iglesias-Ussel MD, Roa S, Kalis SL et al. (2008) The biochemistry of somatic hypermutation. Annu Rev Immunol 26: 481-511. doi:10.1146/annurev.immunol.26.021607.090236. PubMed: 18304001.
[2]  Stavnezer J, Guikema JE, Schrader CE (2008) Mechanism and regulation of class switch recombination. Annu Rev Immunol 26: 261-292. doi:10.1146/annurev.immunol.26.021607.090248. PubMed: 18370922.
[3]  Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y et al. (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102: 553-563. doi:10.1016/S0092-8674(00)00078-7. PubMed: 11007474.
[4]  Revy P, Muto T, Levy Y, Geissmann F, Plebani A et al. (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102: 565-575. doi:10.1016/S0092-8674(00)00079-9. PubMed: 11007475.
[5]  Smith HC, Bennett RP, Kizilyer A, McDougall WM, Prohaska KM (2012) Functions and regulation of the APOBEC family of proteins. Semin Cell Dev Biol 23: 258-268. doi:10.1016/j.semcdb.2011.10.004. PubMed: 22001110.
[6]  Imai K, Slupphaug G, Lee WI, Revy P, Nonoyama S et al. (2003) Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 4: 1023-1028. doi:10.1038/ni974. PubMed: 12958596.
[7]  Di Noia J, Neuberger MS (2002) Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 419: 43-48. doi:10.1038/nature00981. PubMed: 12214226.
[8]  Masani S, Han L, Yu K (2013) Apurinic/Apyrimidinic Endonuclease 1 Is the Essential Nuclease during Immunoglobulin Class Switch Recombination. Mol Cell Biol 33: 1468-1473. doi:10.1128/MCB.00026-13. PubMed: 23382073.
[9]  Guikema JE, Linehan EK, Tsuchimoto D, Nakabeppu Y, Strauss PR et al. (2007) APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination. J Exp Med 204: 3017-3026. doi:10.1084/jem.20071289. PubMed: 18025127.
[10]  Arudchandran A, Bernstein RM, Max EE (2004) Single-stranded DNA breaks adjacent to cytosines occur during Ig gene class switch recombination. J Immunol 173: 3223-3229. PubMed: 15322184.
[11]  Rush JS, Fugmann SD, Schatz DG (2004) Staggered AID-dependent DNA double strand breaks are the predominant DNA lesions targeted to S mu in Ig class switch recombination. Int Immunol 16: 549-557. doi:10.1093/intimm/dxh057. PubMed: 15039385.
[12]  Petersen S, Casellas R, Reina-San-Martin B, Chen HT, Difilippantonio MJ, et al. (2001) AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature 414: 660-665.
[13]  Boboila C, Alt FW, Schwer B (2012) Classical and alternative end-joining pathways for repair of lymphocyte-specific and general DNA double-strand breaks. Adv Immunol 116: 1-49. doi:10.1016/B978-0-12-394300-2.00001-6. PubMed: 23063072.
[14]  Arakawa H, Moldovan GL, Saribasak H, Saribasak NN, Jentsch S et al. (2006) A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS Biol 4: e366. doi:10.1371/journal.pbio.0040366. PubMed: 17105346.
[15]  Martomo SA, Yang WW, Gearhart PJ (2004) A role for Msh6 but not Msh3 in somatic hypermutation and class switch recombination. J Exp Med 200: 61-68. doi:10.1084/jem.20040691. PubMed: 15238605.
[16]  Martin A, Li Z, Lin DP, Bardwell PD, Iglesias-Ussel MD et al. (2003) Msh2 ATPase activity is essential for somatic hypermutation at a-T basepairs and for efficient class switch recombination. J Exp Med 198: 1171-1178. doi:10.1084/jem.20030880. PubMed: 14568978.
[17]  Rada C, Jarvis JM, Milstein C (2002) AID-GFP chimeric protein increases hypermutation of Ig genes with no evidence of nuclear localization. Proc Natl Acad Sci U S A 99: 7003-7008. doi:10.1073/pnas.092160999. PubMed: 12011459.
[18]  Faili A, Aoufouchi S, Weller S, Vuillier F, Stary A et al. (2004) DNA polymerase eta is involved in hypermutation occurring during immunoglobulin class switch recombination. J Exp Med 199: 265-270. doi:10.1084/jem.20031831. PubMed: 14734526.
[19]  Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK (2004) Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming. J Biol Chem 279: 52353-52360. doi:10.1074/jbc.M407695200. PubMed: 15448152.
[20]  Cortellino S, Xu J, Sannai M, Moore R, Caretti E et al. (2011) Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair. Cell 146: 67-79. doi:10.1016/j.cell.2011.06.020. PubMed: 21722948.
[21]  Guo JU, Su Y, Zhong C, Ming GL, Song H (2011) Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145: 423-434. doi:10.1016/j.cell.2011.03.022. PubMed: 21496894.
[22]  Rangam G, Schmitz KM, Cobb AJ, Petersen-Mahrt SK (2012) AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud. PLOS ONE 7: e43279. doi:10.1371/journal.pone.0043279. PubMed: 22916236.
[23]  Wijesinghe P, Bhagwat AS (2012) Efficient deamination of 5-methylcytosines in DNA by human APOBEC3A, but not by AID or APOBEC3G. Nucleic Acids Res 40: 9206-9217. doi:10.1093/nar/gks685. PubMed: 22798497.
[24]  Nabel CS, Jia H, Ye Y, Shen L, Goldschmidt HL et al. (2012) AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation. Nat Chem Biol 8: 751-758. doi:10.1038/nchembio.1042. PubMed: 22772155.
[25]  Kim YJ, Wilson DM 3rd (2012) Overview of base excision repair biochemistry. Curr Mol Pharmacol 5: 3-13. doi:10.2174/1874467211205010003. PubMed: 22122461.
[26]  Hasham MG, Donghia NM, Coffey E, Maynard J, Snow KJ et al. (2010) Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination. Nat Immunol 11: 820-826. doi:10.1038/ni.1909. PubMed: 20657597.
[27]  Popp C, Dean W, Feng S, Cokus SJ, Andrews S et al. (2010) Genome-wide erasure of DNA methylation in mouse primordial germ cells is affected by AID deficiency. Nature 463: 1101-1105. doi:10.1038/nature08829. PubMed: 20098412.
[28]  Bhutani N, Brady JJ, Damian M, Sacco A, Corbel SY et al. (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation. Nature 463: 1042-1047. doi:10.1038/nature08752. PubMed: 20027182.
[29]  Bhutani N, Decker MN, Brady JJ, Bussat RT, Burns DM et al. (2013) A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells. FASEB J 27: 1107-1113. doi:10.1096/fj.12-222125. PubMed: 23212122.
[30]  Kumar R, Dimenna L, Schrode N, Liu TC, Franck P et al. (2013) AID stabilizes stem-cell phenotype by removing epigenetic memory of pluripotency genes. Nature, 500: 89–92. PubMed: 23803762.
[31]  Mu?oz DP, Lee EL, Takayama S, Coppé JP, Heo SJ et al. (2013) Activation-induced cytidine deaminase (AID) is necessary for the epithelial-mesenchymal transition in mammary epithelial cells. Proc Natl Acad Sci U S A 110: E2977-E2986. doi:10.1073/pnas.1301021110. PubMed: 23882083.
[32]  Rai K, Huggins IJ, James SR, Karpf AR, Jones DA et al. (2008) DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 135: 1201-1212. doi:10.1016/j.cell.2008.11.042. PubMed: 19109892.
[33]  Patenaude AM, Orthwein A, Hu Y, Campo VA, Kavli B et al. (2009) Active nuclear import and cytoplasmic retention of activation-induced deaminase. Nat Struct Mol Biol 16: 517-527. doi:10.1038/nsmb.1598. PubMed: 19412186.
[34]  McBride KM, Barreto V, Ramiro AR, Stavropoulos P, Nussenzweig MC (2004) Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase. J Exp Med 199: 1235-1244. doi:10.1084/jem.20040373. PubMed: 15117971.
[35]  Ito S, Nagaoka H, Shinkura R, Begum N, Muramatsu M et al. (2004) Activation-induced cytidine deaminase shuttles between nucleus and cytoplasm like apolipoprotein B mRNA editing catalytic polypeptide 1. Proc Natl Acad Sci U S A 101: 1975-1980. doi:10.1073/pnas.0307335101. PubMed: 14769937.
[36]  H?sler J, Rada C, Neuberger MS (2011) Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1alpha (eEF1A). Proc Natl Acad Sci U S A 108: 18366-18371. doi:10.1073/pnas.1106729108. PubMed: 22042842.
[37]  Aoufouchi S, Faili A, Zober C, D'Orlando O, Weller S et al. (2008) Proteasomal degradation restricts the nuclear lifespan of AID. J Exp Med 205: 1357-1368. doi:10.1084/jem.20070950. PubMed: 18474627.
[38]  Uchimura Y, Barton LF, Rada C, Neuberger MS (2011) REG-gamma associates with and modulates the abundance of nuclear activation-induced deaminase. J Exp Med 208: 2385-2391. doi:10.1084/jem.20110856. PubMed: 22042974.
[39]  Geisberger R, Rada C, Neuberger MS (2009) The stability of AID and its function in class-switching are critically sensitive to the identity of its nuclear-export sequence. Proc Natl Acad Sci U S A 106: 6736-6741. doi:10.1073/pnas.0810808106. PubMed: 19351893.
[40]  Zaprazna K, Atchison ML (2012) YY1 controls immunoglobulin class switch recombination and nuclear activation-induced deaminase levels. Mol Cell Biol 32: 1542-1554. doi:10.1128/MCB.05989-11. PubMed: 22290437.
[41]  Yoshikawa K, Okazaki IM, Eto T, Kinoshita K, Muramatsu M et al. (2002) AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science 296: 2033-2036. doi:10.1126/science.1071556. PubMed: 12065838.
[42]  Okazaki IM, Kinoshita K, Muramatsu M, Yoshikawa K, Honjo T (2002) The AID enzyme induces class switch recombination in fibroblasts. Nature 416: 340-345. doi:10.1038/nature727. PubMed: 11875397.
[43]  Martin A, Bardwell PD, Woo CJ, Fan M, Shulman MJ et al. (2002) Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature 415: 802-806. doi:10.1038/nature714. PubMed: 11823785.
[44]  Maeda K, Singh SK, Eda K, Kitabatake M, Pham P et al. (2010) GANP-mediated recruitment of activation-induced cytidine deaminase to cell nuclei and to immunoglobulin variable region. DNA - J Biol Chem 285: 23945-23953. doi:10.1074/jbc.M110.131441.
[45]  Cattoretti G, Büttner M, Shaknovich R, Kremmer E, Alobeid B et al. (2006) Nuclear and cytoplasmic AID in extrafollicular and germinal center B cells. Blood 107: 3967-3975. doi:10.1182/blood-2005-10-4170. PubMed: 16439679.
[46]  Schreck S, Buettner M, Kremmer E, Bogdan M, Herbst H et al. (2006) Activation-induced cytidine deaminase (AID) is expressed in normal spermatogenesis but only infrequently in testicular germ cell tumours. J Pathol 210: 26-31. doi:10.1002/path.2014. PubMed: 16783758.
[47]  Brar SS, Watson M, Diaz M (2004) Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks. J Biol Chem 279: 26395-26401. doi:10.1074/jbc.M403503200. PubMed: 15087440.
[48]  Ward JF, Evans JW, Limoli CL, Calabro-Jones PM (1987) Radiation and hydrogen peroxide induced free radical damage to DNA. Br J Cancer Suppl 8: 105-112. PubMed: 2820457.
[49]  Montecucco A, Biamonti G (2007) Cellular response to etoposide treatment. Cancer Lett 252: 9-18. doi:10.1016/j.canlet.2006.11.005. PubMed: 17166655.
[50]  Chow KC, Ross WE (1987) Topoisomerase-specific drug sensitivity in relation to cell cycle progression. Mol Cell Biol 7: 3119-3123. PubMed: 2823120.
[51]  Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T et al. (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106: 348-360. doi:10.1007/s004120050256. PubMed: 9362543.
[52]  Yang J, Bardes ES, Moore JD, Brennan J, Powers MA et al. (1998) Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev 12: 2131-2143. doi:10.1101/gad.12.14.2131. PubMed: 9679058.
[53]  Pines J, Hunter T (1991) Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport. J Cell Biol 115: 1-17. doi:10.1083/jcb.115.1.1. PubMed: 1717476.
[54]  Hajji N, Pastor N, Mateos S, Domínguez I, Cortés F (2003) DNA strand breaks induced by the anti-topoisomerase II bis-dioxopiperazine ICRF-193. Mutat Res 530: 35-46. doi:10.1016/S0027-5107(03)00135-0. PubMed: 14563529.
[55]  Huang KC, Gao H, Yamasaki EF, Grabowski DR, Liu S et al. (2001) Topoisomerase II poisoning by ICRF-193. J Biol Chem 276: 44488-44494. doi:10.1074/jbc.M104383200. PubMed: 11577077.
[56]  Roca J, Ishida R, Berger JM, Andoh T, Wang JC (1994) Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp. Proc Natl Acad Sci U S A 91: 1781-1785. doi:10.1073/pnas.91.5.1781. PubMed: 8127881.
[57]  Barreto V.Reina-San-Martin B, Ramiro AR, McBride KM, Nussenzweig MC (2003) C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion. Mol Cell 12: 501-508.
[58]  Ellyard JI, Benk AS, Taylor B, Rada C, Neuberger MS (2011) The dependence of Ig class-switching on the nuclear export sequence of AID likely reflects interaction with factors additional to Crm1 exportin. Eur J Immunol 41: 485-490. doi:10.1002/eji.201041011. PubMed: 21268017.
[59]  Ta VT, Nagaoka H, Catalan N, Durandy A, Fischer A et al. (2003) AID mutant analyses indicate requirement for class-switch-specific cofactors. Nat Immunol 4: 843-848. doi:10.1038/ni964. PubMed: 12910268.
[60]  Mu Y, Prochnow C, Pham P, Chen XS, Goodman MF (2012) A structural basis for the biochemical behavior of activation-induced deoxycytidine deaminase class-switch recombination-defective hyper-IgM-2 mutants. J Biol Chem 287: 28007-28016. doi:10.1074/jbc.M112.370189. PubMed: 22715099.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133