%0 Journal Article
%T The radioresistance kinase TLK1B protects the cells by promoting repair of double strand breaks
%A Gulshan Sunavala-Dossabhoy
%A Sri Balakrishnan
%A Siddhartha Sen
%A Sam Nuthalapaty
%A Arrigo De Benedetti
%J BMC Molecular Biology
%D 2005
%I BioMed Central
%R 10.1186/1471-2199-6-19
%X In this work, we provide several lines of evidence that TLK1B protects the cells from IR by facilitating the repair of DSBs. First, the pattern of phosphorylation and dephosphorylation of H2AX and H3 indicated that cells overexpressing TLK1B return to pre-IR steady state much more rapidly than controls. Second, the repair of episomes damaged with DSBs was much more rapid in cells overexpressing TLK1B. This was also true for repair of genomic damage. Lastly, we demonstrate with an in vitro repair system that the addition of recombinant TLK1B promotes repair of a linearized plasmid incubated with nuclear extract. In addition, TLK1B in this in vitro system promotes the assembly of chromatin as shown by the formation of more highly supercoiled topomers of the plasmid.In this work, we provide evidence that TLK1B promotes the repair of DSBs, likely as a consequence of a change in chromatin remodeling capacity that must precede the assembly of repair complexes at the sites of damage.The Tousled gene of Arabidopsis thaliana encodes a protein kinase which, when mutated, results in abnormal flower development characterized by a stochastic loss of floral meristem and organs [1]. Two mammalian Tousled-like kinases (TLK1 and TLK2) were cloned by Sillje et al., 1999 [2] during a PCR-based search for human kinases, who also reported that the activity of these kinases is maximal in S phase, and more recently, these kinases were reported to be targets of checkpoint kinases, ATM and Chk1 [3]. Specifically, it was reported that TLK1 is inhibited by Chk1 by direct phosphorylation at S695. These findings identify a functional cooperation between ATM and Chk1 in propagation of a checkpoint response to DNA damage and suggest that through transient inhibition of TLK1 the ATM-CHK1-TLK pathway may regulate processes involved in chromatin assembly [4]. Indeed, in AT cells (cells deficient in ATM protein) TLK1 was not inhibited after genotoxic stress [4]. Since ATM and Chk1 are involved in the
%U http://www.biomedcentral.com/1471-2199/6/19