DNA Damage Responses That Enhance Resilience to Replication Stress

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2021 Aug 31

PMID 34463774

Citations 9

Authors

Kazumasa Yoshida

Masatoshi Fujita

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ.

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes.

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DNA replication: Mechanisms and therapeutic interventions for diseases.

Song H, Shen R, Mahasin H, Guo Y, Wang D MedComm (2020). 2023; 4(1):e210.

PMID: 36776764 PMC: 9899494. DOI: 10.1002/mco2.210.

Microscopic Detection of DNA Synthesis in Early Mitosis at Repetitive Sequences in Human Cells.

Yoshida K, Ishimoto R, Fujita M Bio Protoc. 2022; 12(17).

PMID: 36213106 PMC: 9501721. DOI: 10.21769/BioProtoc.4504.

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