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Human RECQL5 overcomes thymidine-induced replication stress

Authors
Journal
DNA Repair
1568-7864
Publisher
Elsevier
Publication Date
Volume
9
Issue
9
Identifiers
DOI: 10.1016/j.dnarep.2010.06.009
Keywords
  • Homologous Recombination
  • Thymidine
  • Recql5
  • Replication
Disciplines
  • Biology

Abstract

Abstract Accurate DNA replication is essential to genome integrity and is controlled by five human RecQ helicases, of which at least three prevent cancer and ageing. Here, we have studied the role of RECQL5, which is the least characterised of the five human RecQ helicases. We demonstrate that overexpressed RECQL5 promotes survival during thymidine-induced slowing of replication forks in human cells. The RECQL5 protein relocates specifically to stalled replication forks and suppresses thymidine-induced RPA foci, CHK1 signalling, homologous recombination and γH2AX activation. It is unlikely that RECQL5 promotes survival through translesion synthesis as PCNA ubiquitylation is also reduced. Interestingly, we also found that overexpressing RECQL5 relieves cells of the cell cycle arrest normally imposed by thymidine, but without causing mutations. In conclusion, we propose that RECQL5 stabilises the replication fork allowing replication to overcome the effects of thymidine and complete the cell cycle.

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