Premium
The role of ATM signalling in DNA double strand break repair.
Author(s) -
Jeggo Penelope Ann,
Goodarzi Aaron A,
Shibata Atsushi,
Lobrich Markus
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.411.1
Subject(s) - chromatin , microbiology and biotechnology , homologous recombination , heterochromatin , nuclease , dna , dna repair , homology directed repair , biology , chemistry , genetics , nucleotide excision repair
DNA double strand breaks (DSBs) induced by ionizing radiation are repaired with fast and slow kinetics. The slow component of DSB repair represents the repair of DSBs located close to or within regions of heterochromatin (HC), demonstrating that HC provides a barrier to DSB repair. These DSBs specifically require ATM, the nuclease, Artemis, and mediator proteins involved in ATM signaling. ATM phosphorylates the heterochromatic building factor, Kap1, and phosphorylated Kap1 changes its chromatin binding capacity. The available evidence suggests that ATM modifies Kap1 to promote chromatin relaxation in the vicinity of the DSB to allow DSB repair. The mediator protein, 53BP1, is dispensable for pan nuclear Kap1 phosphorylation but is specifically required for p‐Kap1 foci formation, which specifically occurs at DSBs located at HC regions. We propose that this allows concentrated changes in Kap1 at the site of the DSB. Following these chromatin modifications, the DSBs are repaired by a process involving the DNA non‐homologous end‐joining proteins in G1 phase but by homologous recombination in G2 phase.