Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation

被引:197
作者
Griffin, CS [1 ]
Simpson, PJ [1 ]
Wilson, CR [1 ]
Thacker, J [1 ]
机构
[1] MRC, Radiat & Genome Stabil Unit, Didcot OX11 0RD, Oxon, England
关键词
D O I
10.1038/35036399
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Growth and development are dependent on the faithful duplication of cells. Duplication requires accurate genome replication, the repair of any DNA damage, and the precise segregation of chromosomes at mitosis; molecular checkpoints ensure the proper progression and fidelity of each stage. Loss of any of these highly conserved functions may result in genetic instability and proneness to cancer. Here we show that highly significant increases in chromosome missegregation occur in cell lines lacking the RAD51-like genes XRCC2 and XRCC3. This increased missegregation is associated with fragmentation of the centrosome, a component of the mitotic spindle, and not with loss of the spindle checkpoint. Our results show that unresolved DNA damage triggers this instability, and that XRCC2 and XRCC3 are potential tumour-suppressor genes in mammals.
引用
收藏
页码:757 / 761
页数:5
相关论文
共 30 条
[11]   BRCA1 is associated with the centrosome during mitosis [J].
Hsu, LC ;
White, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :12983-12988
[12]   DNA breakage and repair [J].
Jeggo, PA .
ADVANCES IN GENETICS, VOL 38, 1998, 38 :185-218
[13]   Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination [J].
Johnson, RD ;
Liu, N ;
Jasin, M .
NATURE, 1999, 401 (6751) :397-399
[14]   Genetic instability in colorectal cancers [J].
Lengauer, C ;
Kinzler, KW ;
Vogelstein, B .
NATURE, 1997, 386 (6625) :623-627
[15]   Altered centrosome structure is associated with abnormal mitoses in human breast tumors [J].
Lingle, WL ;
Salisbury, JL .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 155 (06) :1941-1951
[16]   XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages [J].
Liu, N ;
Lamerdin, JE ;
Tebbs, RS ;
Schild, D ;
Tucker, JD ;
Shen, MR ;
Brookman, KW ;
Siciliano, MJ ;
Walter, CA ;
Fan, WF ;
Narayana, LS ;
Zhou, ZQ ;
Adamson, AW ;
Sorensen, KJ ;
Chen, DJ ;
Jones, NJ ;
Thompson, LH .
MOLECULAR CELL, 1998, 1 (06) :783-793
[17]   Brca1 controls homology-directed DNA repair [J].
Moynahan, ME ;
Chiu, JW ;
Koller, BH ;
Jasin, M .
MOLECULAR CELL, 1999, 4 (04) :511-518
[18]   XRCC3 promotes homology-directed repair of DNA damage in mammalian cells [J].
Pierce, AJ ;
Johnson, RD ;
Thompson, LH ;
Jasin, M .
GENES & DEVELOPMENT, 1999, 13 (20) :2633-2638
[19]  
Pihan GA, 1998, CANCER RES, V58, P3974
[20]   CLASSIFICATION AND RELATIONSHIPS OF INDUCED CHROMOSOMAL STRUCTURAL-CHANGES [J].
SAVAGE, JRK .
JOURNAL OF MEDICAL GENETICS, 1976, 13 (02) :103-122