Journal Article

DNA damage responses and their many interactions with the replication fork

Paul R. Andreassen, Gary P.H. Ho and Alan D. D'Andrea

in Carcinogenesis

Volume 27, issue 5, pages 883-892
Published in print May 2006 | ISSN: 0143-3334
Published online February 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi319
DNA damage responses and their many interactions with the replication fork

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The cellular response to DNA damage is composed of cell cycle checkpoint and DNA repair mechanisms that serve to ensure proper replication of the genome prior to cell division. The function of the DNA damage response during DNA replication in S-phase is critical to this process. Recent evidence has suggested a number of interrelationships of DNA replication and cellular DNA damage responses. These include S-phase checkpoints which suppress replication initiation or elongation in response to DNA damage. Also, many components of the DNA damage response are required either for the stabilization of, or for restarting, stalled replication forks. Further, translesion synthesis permits DNA replication to proceed in the presence of DNA damage and can be coordinated with subsequent repair by homologous recombination (HR). Finally, cohesion of sister chromatids is established coincident with DNA replication and is required for subsequent DNA repair by homologous recombination. Here we review these processes, all of which occur at, or are related to, the advancing replication fork. We speculate that these multiple interdependencies of DNA replication and DNA damage responses integrate the many steps necessary to ensure accurate duplication of the genome.

Keywords: ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3-related; BLM, Bloom syndrome; BRCA1 and 2, BReast CAncer genes/proteins 1 and 2; DSBs, double-strand DNA breaks; FANCD1 and FANCD2, Fanconi anemia proteins D1 and D2; HR, homologous recombination; IR, ionizing radiation; NBS, Nijmegen breakage syndrome; SMC, structural maintenance of chromosomes; TLS, translesion synthesis; UVC, ultraviolet irradiation

Journal Article.  7553 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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