GENE DISRUPTION OF A G4-DNA-DEPENDENT NUCLEASE IN YEAST LEADS TO CELLULAR SENESCENCE AND TELOMERE SHORTENING

被引:65
作者
LIU, ZP
LEE, A
GILBERT, W
机构
[1] Dept. of Molec. and Cellular Biology, Biological Laboratories, Harvard University, Cambridge, MA 02138-2092
关键词
GUANINE-QUARTET; KEM1; SEP1; CHECKPOINT; MEIOSIS;
D O I
10.1073/pnas.92.13.6002
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 ; 0710 ; 09 ;
摘要
The yeast gene KEM1 (also named SEP1/DST2/XRN1/RAR5) produces a G4-DNA-dependent nuclease that binds to G4 tetraplex DNA structure and cuts in a single-stranded region 5' to the G4 structure. G4-DNA generated from yeast telomeric oligonucleotides competitively inhibits the cleavage reaction, suggesting that this enzyme may interact with yeast telomeres in vivo. Homozygous deletions of the KEM1 gene in yeast block meiosis at the pachytene stage, which is consistent with the hypothesis that G4 tetraplex DNA may be involved in homologous chromosome pairing during meiosis. We conjectured that the mitotic defects of kem1/sep1 mutant cells, such as a higher chromosome loss rate, are also due to failure in processing G4-DNA, especially at telomeres. Here we report two phenotypes associated with a kem1-null allele, cellular senescence and telomere shortening, that provide genetic evidence that G4 tetraplex DNA may play a role in telomere functioning. In addition, our results reveal that chromosome ends in the same cells behave differently in a fashion dependent on the KEM1 gene product.
引用
收藏
页码:6002 / 6006
页数:5
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