MRT-2 checkpoint protein is required for germline immortality and telomere replication in C-elegans

被引:226
作者
Ahmed, S [1 ]
Hodgkin, J [1 ]
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
D O I
10.1038/35003120
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 [理学]; 0710 [生物学]; 09 [农学];
摘要
The germ line is an immortal cell lineage that is passed indefinitely from one generation to the next. To identify the genes that are required for germline immortality, we isolated Caenorhabditis elegans mutants with mortal germ lines-worms that can reproduce for several healthy generations but eventually become sterile. One of these mortal germline (mrt) mutants, mrt-2, exhibits progressive telomere shortening and accumulates end-to-end chromosome fusions in later generations, indicating that the MRT-2 protein is required for telomere replication. In addition, the germ line of mrt-2 is hypersensitive to X-rays and to transposon activity. Therefore, mrt-2 has defects in responding both to damaged DNA and to normal double-strand breaks present at telomeres. mrt-2 encodes a homologue of a checkpoint gene that is required to sense DMA damage in yeast. These results indicate that telomeres may be identified as a type of DNA damage and then repaired by the telomere-replication enzyme telomerase.
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页码:159 / 164
页数:6
相关论文
共 50 条
[1]
Segregation of holocentric chromosomes at meiosis in the nematode, Caenorhabditis elegans [J].
Albertson, Donna G. ;
Thomson, J. Nichol .
CHROMOSOME RESEARCH, 1993, 1 (01) :15-26
[2]
DNA-REPAIR MUTANTS DEFINING G2 CHECKPOINT PATHWAYS IN SCHIZOSACCHAROMYCES-POMBE [J].
ALKHODAIRY, F ;
CARR, AM .
EMBO JOURNAL, 1992, 11 (04) :1343-1350
[3]
Anderson P, 1995, METHOD CELL BIOL, V48, P31
[4]
Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[5]
A human and mouse homolog of the Schizosaccharomyces pombe rad1+ cell cycle checkpoint control gene [J].
Bluyssen, HAR ;
van Os, RI ;
Naus, NC ;
Jaspers, I ;
Hoeijmakers, JHJ ;
de Klein, A .
GENOMICS, 1998, 54 (02) :331-337
[6]
Identification of a Saccharomyces cerevisiae Ku80 homologue: Roles in DNA double strand break rejoining and in telomeric maintenance [J].
Boulton, SJ ;
Jackson, SP .
NUCLEIC ACIDS RESEARCH, 1996, 24 (23) :4639-4648
[7]
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
[8]
p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis [J].
Chin, L ;
Artandi, SE ;
Shen, Q ;
Tam, A ;
Lee, SL ;
Gottlieb, GJ ;
Greider, CW ;
DePinho, RA .
CELL, 1999, 97 (04) :527-538
[9]
Regulation of telomere length by checkpoint genes in Schizosaccharomyces pombe [J].
Dahlén, M ;
Olsson, T ;
Kanter-Smoler, G ;
Ramne, A ;
Sunnerhagen, P .
MOLECULAR BIOLOGY OF THE CELL, 1998, 9 (03) :611-621
[10]
CDNA cloning and Gene Mapping of Human Homologs for Schizosaccharomyces pombe rad17, rad1, and hus1 and cloning of homologs from mouse, Caenorhabditis elegans, and Drosophila melanogaster [J].
Dean, FB ;
Lian, LB ;
O'Donnell, M .
GENOMICS, 1998, 54 (03) :424-436