Rad54 and DNA Ligase IV cooperate to maintain mammalian chromatid stability

被引:101
作者
Mills, KD
Ferguson, DO
Essers, J
Eckersdorff, M
Kanaar, R
Alt, FW [1 ]
机构
[1] CBR Inst Biomed Res, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
[3] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[4] Erasmus MC, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands
[5] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA
关键词
DNA break repair; nonhomologous end joining; homologous recombination; Lig4; Rad54;
D O I
10.1101/gad.1204304
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Nonhomologous end joining (NHEJ) and homologous recombination (HR) represent the two major pathways of DNA double-strand break (DSB) repair in eukaryotic cells. NHEJ repairs DSBs by ligation of cognate broken ends irrespective of homologous flanking sequences, whereas HR repairs DSBs using an undamaged homologous template. Although both NHEJ and HR have been clearly implicated in the maintenance of genome stability, how these apparently independent and mechanistically distinct pathways are coordinated remains largely unexplored. To investigate the relationship between HR and NHEJ modes of DSB repair, we generated cells doubly deficient for the NHEJ factor DNA Ligase IV (Lig4) and the HR factor Rad54. We show that Lig4 and Rad54 cooperate to support cellular proliferation, repair spontaneous DSBs, and prevent chromosome and single chromatid aberrations. These findings demonstrate a role for NHEJ in the repair of DSBs that occur spontaneously during or after DNA replication, and reveal overlapping functions for NHEJ and Rad54-dependent HR in the repair of such DSBs.
引用
收藏
页码:1283 / 1292
页数:10
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