hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases
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The maintenance of genomic stability is essential for cellular viability and the prevention of diseases such as cancer. Human single-stranded DNA-binding protein 1 (hSSB1) is a protein with roles in the stabilisation and restart of stalled DNA replication forks, as well as in the repair of oxidative DNA lesions and double-strand DNA breaks. In the latter process, phosphorylation of threonine 117 by the ATM kinase is required for hSSB1 stability and efficient DNA repair. The regulation of hSSB1 in other DNA repair pathways has however remained unclear. Here we report that hSSB1 is also directly phosphorylated by DNA-PK at serine residue 134. While this modification is largely suppressed in undamaged cells by PPP-family protein phosphatases, S134 phosphorylation is enhanced following the disruption of replication forks and promotes cellular survival. Together, these data thereby represent a novel mechanism for hSSB1 regulation following the inhibition of replication.
Ashton , N W , Paquet , N , Shirran , S L , Bolderson , E , Kariawasam , R , Touma , C , Fallahbaghery , A , Gamsjaeger , R , Cubeddu , L , Botting , C , Pollock , P M , O’Byrne , K J & Richard , D J 2017 , ' hSSB1 phosphorylation is dynamically regulated by DNA-PK and PPP-family protein phosphatases ' DNA Repair , vol. 54 , pp. 30-39 . DOI: 10.1016/j.dnarep.2017.03.006
© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
DescriptionThis work was supported by a National Health and Medical Research Council project grant , an Australian Research Council project grant [DP 120103099] and by a Queensland Health Senior Clinical Research Fellowship awarded to K.J.O. This work was also supported by the Wellcome Trust [094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews. NWA was supported by a scholarship awarded by Cancer Council Queensland. E.B. is supported by an Advance Queensland Research Fellowship.
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