DNA damage responses that enhance resilience to replication stress

Kazumasa Yoshida, Masatoshi Fujita

研究成果: Contribution to journalReview article査読

2 被引用数 (Scopus)

抄録

During duplication of the genome, eukaryotic cells may experience various exogenous and endogenous replication stresses that impede progression of DNA replication along chromosomes. Chemical alterations in template DNA, imbalances of deoxynucleotide pools, repetitive sequences, tight DNA–protein complexes, and conflict with transcription can negatively affect the replication machineries. If not properly resolved, stalled replication forks can cause chromosome breaks leading to genomic instability and tumor development. Replication stress is enhanced in cancer cells due, for example, to the loss of DNA repair genes or replication–transcription conflict caused by activation of oncogenic pathways. To prevent these serious consequences, cells are equipped with diverse mechanisms that enhance the resilience of replication machineries to replication stresses. This review describes DNA damage responses activated at stressed replication forks and summarizes current knowledge on the pathways that promote faithful chromosome replication and protect chromosome integrity, including ATR-dependent replication checkpoint signaling, DNA cross-link repair, and SLX4-mediated responses to tight DNA–protein complexes that act as barriers. This review also focuses on the relevance of replication stress responses to selective cancer chemotherapies.

本文言語英語
ページ(範囲)6763-6773
ページ数11
ジャーナルCellular and Molecular Life Sciences
78
21-22
DOI
出版ステータス出版済み - 11 2021

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 分子生物学
  • 薬理学
  • 細胞および分子神経科学
  • 細胞生物学

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