Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories

Xin Quan Ge, J. Julian Blow

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168 Citations (Scopus)


Replication origins are licensed by loading MCM2-7 hexamers before entry into S phase. However, only similar to 10% of licensed origins are normally used in S phase, with the others remaining dormant. When fork progression is inhibited, dormant origins initiate nearby to ensure that all of the DNA is eventually replicated. In apparent contrast, replicative stress activates ataxia telangiectasia and rad-3-related (ATR) and Chk1 checkpoint kinases that inhibit origin firing. In this study, we show that at low levels of replication stress, ATR/Chk1 predominantly suppresses origin initiation by inhibiting the activation of new replication factories, thereby reducing the number of active factories. At the same time, inhibition of replication fork progression allows dormant origins to initiate within existing replication factories. The inhibition of new factory activation by ATR/Chk1 therefore redirects replication toward active factories where forks are inhibited and away from regions that have yet to start replication. This minimizes the deleterious consequences of fork stalling and prevents similar problems from arising in unreplicated regions of the genome.
Original languageEnglish
Pages (from-to)1285-1297
Number of pages13
JournalJournal of Cell Biology
Issue number7
Publication statusPublished - 20 Dec 2010

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