Controlling DNA replication origins in response to DNA damage - inhibit globally, activate locally

M. Yekezare, B. Gomez-Gonzalez, J. F. X. Diffley
2013 Journal of Cell Science  
DNA replication in eukaryotic cells initiates from multiple replication origins that are distributed throughout the genome. Coordinating the usage of these origins is crucial to ensure complete and timely replication of the entire genome precisely once in each cell cycle. Replication origins fire according to a cell-type-specific temporal programme, which is established in the G1 phase of each cell cycle. In response to conditions causing the slowing or stalling of DNA replication forks, the
more » ... ation forks, the programme of origin firing is altered in two contrasting ways, depending on chromosomal context. First, inactive or 'dormant' replication origins in the vicinity of the stalled replication fork become activated and, second, the S phase checkpoint induces a global shutdown of further origin firing throughout the genome. Here, we review our current understanding on the role of dormant origins and the S phase checkpoint in the rescue of stalled forks and the completion of DNA replication in the presence of replicative stress.
doi:10.1242/jcs.096701 pmid:23645160 fatcat:3dhlf7p6uvh6tjkqt3nh6s42wi