Replication fork dynamics and the DNA damage response

Research output: Contribution to journalReview article

Colleges, School and Institutes

Abstract

Prevention and repair of DNA damage is essential for maintenance of genomic stability and cell survival. DNA replication during S-phase can be a source of DNA damage if endogenous or exogenous stresses impair the progression of replication forks. It has become increasingly clear that DNA-damage-response pathways do not only respond to the presence of damaged DNA, but also modulate DNA replication dynamics to prevent DNA damage formation during S-phase. Such observations may help explain the developmental defects or cancer predisposition caused by mutations in DNA-damage-response genes. The present review focuses on molecular mechanisms by which DNA-damage-response pathways control and promote replication dynamics in vertebrate cells. In particular, DNA damage pathways contribute to proper replication by regulating replication initiation, stabilizing transiently stalled forks, promoting replication restart and facilitating fork movement on difficult-to-replicate templates. If replication fork progression fails to be rescued, this may lead to DNA damage and genomic instability via nuclease processing of aberrant fork structures or incomplete sister chromatid separation during mitosis.

Details

Original languageEnglish
Pages (from-to)13-26
Number of pages14
JournalBiochemical Journal
Volume443
Publication statusPublished - 1 Apr 2012

Keywords

  • checkpoint, translesion synthesis, homologous recombination, cell cycle, DNA repair, DNA helicase

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