Chk1 regulates the density of active replication origins during the vertebrate S phase

Maya-Mendoza, A., Petermann, E., Gillespie, D., Caldecott, K. and Jackson, D. (2007) Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO Journal, 26(11), pp. 2719-2731. (doi: 10.1038/sj.emboj.7601714)

Abstract

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 preexisting 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gillespie, Professor David
• Authors: Maya-Mendoza, A., Petermann, E., Gillespie, D., Caldecott, K., and Jackson, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: EMBO Journal
• ISSN: 0261-4189