Human RECQL5 overcomes thymidine-induced replication stress.

DNA Repair
Rachel BlundredHelen E Bryant

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 gammaH2AX 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.

Citations

Oct 21, 2011·Nucleic Acids Research·Mahesh RamamoorthyVilhelm A Bohr
May 1, 2013·Critical Reviews in Biochemistry and Molecular Biology·Venkateswarlu PopuriVilhelm A Bohr
Oct 29, 2010·Cell Cycle·Yuliang Wu, Robert M Brosh
Dec 27, 2012·Molecular Biology Reports·Sarallah Rezazadeh
Jan 12, 2021·Current Genetics·Nafees AhamadYong-Jie Xu
Aug 7, 2020·Molecular Cell·Yahya BenslimaneLea Harrington
Nov 24, 2016·Biophysical Chemistry·Vaclav UrbanPavel Janscak

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