Mechanism of DNA double-strand break repair by non-homologous end joining

被引:242
作者
Hefferin, ML
Tomkinson, AE
机构
[1] Univ Maryland, Sch Med, Radiat Oncol Res Lab, Dept Radiat Oncol, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA
[3] Univ Maryland, Grad Sch, Mol & Cell Biol Grad Program, Baltimore, MD 21201 USA
关键词
double-strand break; non-homologous; DNA;
D O I
10.1016/j.dnarep.2004.12.005
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The repair of DNA double-strand breaks (DSBs) is critical for maintaining genome stability. Although the non-homologous end joining (NHEJ) pathway frequently results in minor changes in DNA sequence at the break site and occasionally the joining of previously unlinked DNA molecules, it is a major contributor to cell survival following exposure of mammalian cells to agents that cause DSBs. This repair mechanism is conserved in lower eukaryotes and in some prokaryotes although the majority of DSBs are repaired by recombinational repair pathways in these organisms. Here we will describe the biochemical properties of NHEJ factors from bacteria, Saccharomyces cerevisiae and mammals, and how physical and functional interactions among these factors co-ordinate the repair of DSBs. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:639 / 648
页数:10
相关论文
共 67 条
[1]   Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system [J].
Aravind, L ;
Koonin, EV .
GENOME RESEARCH, 2001, 11 (08) :1365-1374
[2]   DNA end-joining catalyzed by human cell-free extracts [J].
Baumann, P ;
West, SC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (24) :14066-14070
[3]   Ku selectively transfers between DNA molecules with homologous ends [J].
Bliss, TM ;
Lane, DP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (09) :5765-5773
[4]   Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends [J].
Block, WD ;
Yu, YP ;
Merkle, D ;
Gifford, JL ;
Ding, Q ;
Meek, K ;
Lees-Miller, SP .
NUCLEIC ACIDS RESEARCH, 2004, 32 (14) :4351-4357
[5]   Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways [J].
Boulton, SJ ;
Jackson, SP .
EMBO JOURNAL, 1996, 15 (18) :5093-5103
[6]   Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing [J].
Boulton, SJ ;
Jackson, SP .
EMBO JOURNAL, 1998, 17 (06) :1819-1828
[7]   Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment [J].
Calsou, P ;
Delteil, C ;
Frit, P ;
Droulet, J ;
Salles, B .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 326 (01) :93-103
[8]   DNA looping by Ku and the DNA-dependent protein kinase [J].
Cary, RB ;
Peterson, SR ;
Wang, JT ;
Bear, DG ;
Bradbury, EM ;
Chen, DJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) :4267-4272
[9]   Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks [J].
Chan, DW ;
Chen, BPC ;
Prithivirajsingh, S ;
Kurimasa, A ;
Story, MD ;
Qin, J ;
Chen, DJ .
GENES & DEVELOPMENT, 2002, 16 (18) :2333-2338
[10]   The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit [J].
Chan, DW ;
LeesMiller, SP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (15) :8936-8941