Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks

被引:234
作者
Ramsden, DA [1 ]
Gellert, M [1 ]
机构
[1] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
DNA repair; DNA-PK; Ku70; Ku86; V(D)J recombination;
D O I
10.1093/emboj/17.2.609
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Ku protein binds to DNA ends and is a cofactor for the DNA-dependent protein kinase, Both of these components are involved in DNA double-strand break repair, but it has not been clear if they function indirectly, by sensing DNA damage and activating other factors, or if they are more directly involved in the processing and rejoining of DNA breaks, We demonstrate that intermolecular ligation of DNA fragments is highly dependent on Ku under conditions designed to mimic those existing in the cell. This effect of Ku is specific to eukaryotic DNA ligases, Ku protein, therefore, has an activity consistent with a direct role in rejoining DNA breaks and independent of DNA-dependent protein kinase.
引用
收藏
页码:609 / 614
页数:6
相关论文
共 37 条
[1]   Ku selectively transfers between DNA molecules with homologous ends [J].
Bliss, TM ;
Lane, DP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (09) :5765-5773
[2]   V(D)J recombination in Ku86-deficient mice: Distinct effects on coding, signal, and hybrid joint formation [J].
Bogue, MA ;
Wang, CY ;
Zhu, CM ;
Roth, DB .
IMMUNITY, 1997, 7 (01) :37-47
[3]   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
[4]   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
[5]   Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta [J].
Chan, DW ;
Mody, CH ;
Ting, NSY ;
LeesMiller, SP .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1996, 74 (01) :67-73
[6]   Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV [J].
Critchlow, SE ;
Bowater, RP ;
Jackson, SP .
CURRENT BIOLOGY, 1997, 7 (08) :588-598
[7]   HELA NUCLEAR-PROTEIN RECOGNIZING DNA TERMINI AND TRANSLOCATING ON DNA FORMING A REGULAR DNA MULTIMERIC PROTEIN COMPLEX [J].
DEVRIES, E ;
VANDRIEL, W ;
BERGSMA, WG ;
ARNBERG, AC ;
VANDERVLIET, PC .
JOURNAL OF MOLECULAR BIOLOGY, 1989, 208 (01) :65-78
[8]   RAT-LIVER DNA LIGASES - CATALYTIC PROPERTIES OF A NOVEL FORM OF DNA-LIGASE [J].
ELDER, RH ;
MONTECUCCO, A ;
CIARROCCHI, G ;
ROSSIGNOL, JM .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1992, 203 (1-2) :53-58
[9]  
FALZON M, 1993, J BIOL CHEM, V268, P10546
[10]   THE DNA-DEPENDENT PROTEIN-KINASE - REQUIREMENT FOR DNA ENDS AND ASSOCIATION WITH KU ANTIGEN [J].
GOTTLIEB, TM ;
JACKSON, SP .
CELL, 1993, 72 (01) :131-142