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| Subject Categories: Cell Cycle | Genome Stability & Dynamics |
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| The EMBO Journal
(2007) 26, 2719–2731, doi:10.1038/sj.emboj.7601714 Published online 10 May 2007 |
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| Chk1 regulates the density of active replication origins during the vertebrate S phase |
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| Apolinar Maya-Mendoza1, Eva Petermann2, David A F Gillespie3, Keith W Caldecott2 and Dean A Jackson1 |
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1 Faculty of Life Sciences, University of Manchester, MIB, Manchester, UK 2 Genome damage and Stability Centre, University of Sussex, Falmer, Brighton, UK 3 Beatson Institute for Cancer Research, Cancer Research UK, Glasgow, UK To whom correspondence should be addressed Dean A Jackson, Faculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester M1 7DN, UK. Tel.: +1 0161 306 4255; Fax: +1 0161 306 8918; E-mail: Dean.Jackson@manchester.ac.uk Received 24 October 2006; Accepted 17 April 2007; Published online 10 May 2007. |
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| Abstract |
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| The checkpoint kinase 1 (Chk1) preserves genome integrity when replication is performed on damaged templates. Recently, Chk1 has also been implicated in regulating different aspects of unperturbed S phase. Using mammalian and avian cells with compromised Chk1 activity, we show that an increase in active replicons compensates for inefficient DNA polymerisation. In the absence of damage, loss of Chk1 activity correlates with the frequent stalling and, possibly, collapse of active forks and activation of adjacent, previously suppressed, origins. In human cells, super-activation of replication origins is restricted to pre-existing replication factories. In avian cells, in contrast, Chk1 deletion also correlates with the super-activation of replication factories and loss of temporal continuity in the replication programme. The same phenotype is induced in wild-type avian cells when Chk1 or ATM/ATR is inhibited. These observations show that Chk1 regulates replication origin activation and contributes to S-phase progression in somatic vertebrate cells. |
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| Keywords: checkpoint proteins, DNA foci, DNA replication, replication origins, S-phase programme |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSSleeping policemen for DNA replication? Nature Cell Biology News and Views (01 Jul 2004) RESEARCHChk1 regulates the density of active replication origins during the vertebrate S phase The EMBO Journal Article The EMBO Journal Article The EMBO Journal Article (07 Mar 2007) |
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