DNA damage responses and their many interactions with the replication fork

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...

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Bibliographic Details
Published in:Carcinogenesis (New York) 2006-05, Vol.27 (5), p.883-892
Main Authors: Andreassen, Paul R., Ho, Gary P.H., D'Andrea, Alan D.
Format: Article
Language:English
Subjects:
Animals
ataxia telangiectasia mutated
ATM
ATM and Rad3-related
ATR
Biological and medical sciences
BLM
Bloom syndrome
BRCA1 and 2
BReast CAncer genes/proteins 1 and 2
Carcinogenesis, carcinogens and anticarcinogens
DNA Damage
DNA Repair
DNA Replication
double-strand DNA breaks
DSBs
FANCD1 and FANCD2
Fanconi anemia proteins D1 and D2
homologous recombination
Humans
ionizing radiation
Medical sciences
Models, Biological
Models, Genetic
NBS
Nijmegen breakage syndrome
Recombination, Genetic
S Phase
Sister Chromatid Exchange
SMC
structural maintenance of chromosomes
TLS
translesion synthesis
Tumors
ultraviolet irradiation
UVC
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Summary: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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/bgi319