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Gamma‐irradiated quiescent cells repair directly induced double‐strand breaks but accumulate persistent double‐strand breaks during subsequent DNA replication
Author(s) -
Minakawa Yusuke,
Atsumi Yuko,
Shinohara Akira,
Murakami Yasufumi,
Yoshioka Kenichi
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12381
Subject(s) - rad51 , biology , dna , double strand , dna replication , dna damage , microbiology and biotechnology , dna repair , in vitro , genetics
H2AX is expressed at very low levels in quiescent normal cells in vivo and in vitro . Such cells repair DNA double‐strand breaks (DSBs) induced by γ‐irradiation through a transient stabilization of H2AX. However, the resultant cells accumulate small numbers of irreparable (or persistent) DSBs via an unknown mechanism. We found that quiescent cells that had repaired DSBs directly induced by γ‐rays were prone to accumulate DSBs during the subsequent DNA replication. Unlike directly induced DSBs, secondary DSBs were not efficiently repaired, although Rad51 and 53BP1 were recruited to these sites. H2AX was dramatically stabilized in response to DSBs directly caused by γ‐rays, enabling γH2AX foci formation and DSB repair, whereas H2AX was barely stabilized in response to secondary DSBs, in which γH2AX foci were small and DSBs were not efficiently repaired. Our results show a pathway that leads to the persistent DSB formation after γ‐irradiation.