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Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase

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posted on 2023-06-08, 04:49 authored by Eva Petermann, Apolinar Maya-Mendoza, George Zachos, David A F Gillespie, Dean A Jackson, Keith CaldecottKeith Caldecott
Chk1 protein kinase maintains replication fork stability in metazoan cells in response to DNA damage and DNA replication inhibitors. Here, we have employed DNA fiber labeling to quantify, for the first time, the extent to which Chk1 maintains global replication fork rates during normal vertebrate S phase. We report that replication fork rates in Chk1¿/¿ chicken DT40 cells are on average half of those observed with wild-type cells. Similar results were observed if Chk1 was inhibited or depleted in wild-type DT40 cells or HeLa cells by incubation with Chk1 inhibitor or small interfering RNA. In addition, reduced rates of fork extension were observed with permeabilized Chk1¿/¿ cells in vitro. The requirement for Chk1 for high fork rates during normal S phase was not to suppress promiscuous homologous recombination at replication forks, because inhibition of Chk1 similarly slowed fork progression in XRCC3¿/¿ DT40 cells. Rather, we observed an increased number of replication fibers in Chk1¿/¿ cells in which the nascent strand is single-stranded, supporting the idea that slow global fork rates in unperturbed Chk1¿/¿ cells are associated with the accumulation of aberrant replication fork structures

History

Publication status

  • Published

File Version

  • Published version

Journal

Molecular and Cellular Biology

ISSN

0270-7306

Issue

8

Volume

26

Page range

3319-3326

Pages

8.0

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-08-05

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