Short telomeres induce a DNA damage response in Saccharomyces cerevisiae

被引:146
作者
Ijpma, AS [1 ]
Greider, CW [1 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Grad Program Cellular & Mol Med, Baltimore, MD 21205 USA
关键词
D O I
10.1091/mbc.02-04-0057
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Rac53p phosphorylation. These responses were dependent on RAD24 and MECL suggesting that short telomeres are recognized as DNA damage and signal G2/M arrest.
引用
收藏
页码:987 / 1001
页数:15
相关论文
共 98 条
  • [1] THE SAD1/RAD53 PROTEIN-KINASE CONTROLS MULTIPLE CHECKPOINTS AND DNA DAMAGE-INDUCED TRANSCRIPTION IN YEAST
    ALLEN, JB
    ZHOU, Z
    SIEDE, W
    FRIEDBERG, EC
    ELLEDGE, SJ
    [J]. GENES & DEVELOPMENT, 1994, 8 (20) : 2401 - 2415
  • [2] Telomere shortening and tumor formation by mouse cells lacking telomerase RNA
    Blasco, MA
    Lee, HW
    Hande, MP
    Samper, E
    Lansdorp, PM
    DePinho, RA
    Greider, CW
    [J]. CELL, 1997, 91 (01) : 25 - 34
  • [3] Brachmann CB, 1998, YEAST, V14, P115
  • [4] Altering telomere structure allows telomerase to act in yeast lacking ATM kinases
    Chan, SWL
    Chang, J
    Prescott, J
    Blackburn, EH
    [J]. CURRENT BIOLOGY, 2001, 11 (16) : 1240 - 1250
  • [5] The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae
    Charles, JF
    Jespersen, SL
    Tinker-Kulberg, RL
    Hwang, L
    Szidon, A
    Morgan, DO
    [J]. CURRENT BIOLOGY, 1998, 8 (09) : 497 - 507
  • [6] Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events
    Chen, QJ
    Ijpma, A
    Greider, CW
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (05) : 1819 - 1827
  • [7] Cell cycle regulation of the Saccharomyces cerevisiae polo-like kinase Cdc5p
    Cheng, L
    Hunke, L
    Hardy, CFJ
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (12) : 7360 - 7370
  • [8] p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis
    Chin, L
    Artandi, SE
    Shen, Q
    Tam, A
    Lee, SL
    Gottlieb, GJ
    Greider, CW
    DePinho, RA
    [J]. CELL, 1999, 97 (04) : 527 - 538
  • [9] Collart M.A., 1993, PREPARATION YEAST RN
  • [10] Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression
    Connelly, C
    Hieter, P
    [J]. CELL, 1996, 86 (02) : 275 - 285