IJpma Arne S, Greider Carol W
Department of Molecular Biology and Genetics, Graduate Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mol Biol Cell. 2003 Mar;14(3):987-1001. doi: 10.1091/mbc.02-04-0057.
Telomerase-deficient Saccharomyces cerevisiae cells show a progressive decrease in telomere length. When grown for several days in log phase, the tlc1Delta cells initially display wild-type growth kinetics with subsequent loss of growth potential after which survivors are generated via RAD52-dependent homologous recombination. We found that chromosome loss in these telomerase-deficient cells only increased after a significant decline in growth potential of the culture. At earlier stages of growth, as the telomerase-deficient cells began to show loss of growth potential, the cells arrested in G2/M and showed RNR3 induction and Rad53p phosphorylation. These responses were dependent on RAD24 and MEC1, suggesting that short telomeres are recognized as DNA damage and signal G2/M arrest.
端粒酶缺陷型酿酒酵母细胞的端粒长度呈现出逐渐下降的趋势。当在对数生长期培养数天时,tlc1Delta细胞最初表现出野生型的生长动力学,随后生长潜力丧失,之后通过RAD52依赖的同源重组产生存活细胞。我们发现,在这些端粒酶缺陷型细胞中,染色体丢失仅在培养物生长潜力显著下降后才增加。在生长的早期阶段,随着端粒酶缺陷型细胞开始表现出生长潜力丧失,细胞停滞在G2/M期,并表现出RNR3诱导和Rad53p磷酸化。这些反应依赖于RAD24和MEC1,表明短端粒被识别为DNA损伤并引发G2/M期停滞。