Nucleases Acting at Stalled Forks: How to Reboot the Replication Program with a Few Shortcuts

Philippe Pasero, Alessandro Vindigni

Research output: Contribution to journalReview article

41 Scopus citations

Abstract

In a lifetime, a human being synthesizes approximately 2×1016 meters of DNA, a distance that corresponds to 130,000 times the distance between the Earth and the Sun. This daunting task is executed by thousands of replication forks, which progress along the chromosomes and frequently stall when they encounter DNA lesions, unusual DNA structures, RNA polymerases, or tightly-bound protein complexes. To complete DNA synthesis before the onset of mitosis, eukaryotic cells have evolved complex mechanisms to process and restart arrested forks through the coordinated action of multiple nucleases, topoisomerases, and helicases. In this review, we discuss recent advances in understanding the role and regulation of nucleases acting at stalled forks with a focus on the nucleolytic degradation of nascent DNA, a process commonly referred to as fork resection. We also discuss the effects of deregulated fork resection on genomic instability and on the unscheduled activation of the interferon response under replication stress conditions.

Original languageEnglish
Pages (from-to)477-499
Number of pages23
JournalAnnual Review of Genetics
Volume51
DOIs
StatePublished - Nov 27 2017
Externally publishedYes

Keywords

  • Exonucleases
  • Genomic instability
  • Homologous recombination
  • Replication forks
  • Replication stress
  • Structure-specific nucleases

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