12/21/2007

double strand breaks

Double strand breaks are repaired by either homologous recombination (HR) or by non-homologous end joining (NHEJ), which resembles single-strand break repair (SSBR).

HR employs synthesis-dependent strand annealing (SDSA) and single-strand annealing (SSA).

Enzymes involved:
HR – RecA
NHEJ – DNA ligase IV, Ku-70, Ku-80, DNA-PKCS, XRCC (4-70), Artemis. These proteins presumably evolved, in vertebrates, to participate in the special NHEJ that is required for VDJ recombination. Lymphoid-specific and nonlymphoid-restricted components of the VDJ recombination machinery are also involved in repair of DNA double strand breaks. The nonlymphoid-specific components probably participate in the processing and joining steps of VDJ recombination. [see]

MRC Radiation and Genome Stability Unit: "DNA double-strand breaks (DSBs) are potentially lethal, recombinogenic lesions which can result from exposure to DNA damaging agents such as ionising radiation or endogenous events such as collapsed replication forks. Failure to correctly repair a DSB can result in cell death or tumorigenesis. Indeed many cancer genes have been found to function in DSB metabolism. Eukaryotic cells mount a coordinated response to DSBs which includes cell cycle arrest, DNA repair and transcriptional stress responses. These responses are controlled by the DNA integrity checkpoint, DNA repair and stress-activated MAP kinase pathways, respectively. "

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