Replication Catastrophe: When a Checkpoint Fails because of Exhaustion

Research output: Contribution to journalReviewResearchpeer-review

Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under increased DNA replication stress.

Original languageEnglish
JournalMolecular Cell
Issue number6
Pages (from-to)735-749
Number of pages15
Publication statusPublished - 15 Jun 2017

    Research areas

  • Animals, Cell Death, Cell Proliferation, DNA, DNA Damage, DNA Repair, DNA Replication, Genomic Instability, Humans, Neoplasms, Replication Protein A, Journal Article, Review

ID: 184290876