Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

被引:42
作者
Anderson, Carol M. [1 ]
Korkin, Dmitry [2 ,3 ,4 ]
Smith, Dana L. [1 ]
Makovets, Svetlana [1 ]
Seidel, Jeffrey J. [1 ]
Sali, Andrej [2 ,3 ,4 ]
Blackburn, Elizabeth H. [1 ]
机构
[1] Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Pharmaceut Sci, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94143 USA
关键词
DNA damage signaling; checkpoint; Clk-2; PI3 kinase-like kinase; alpha-superhelical protein; telomere;
D O I
10.1101/gad.1646208
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.
引用
收藏
页码:854 / 859
页数:6
相关论文
共 38 条
  • [1] Cell cycle checkpoint signaling through the ATM and ATR kinases
    Abraham, RT
    [J]. GENES & DEVELOPMENT, 2001, 15 (17) : 2177 - 2196
  • [2] C-elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein
    Ahmed, S
    Alpi, A
    Hengartner, MO
    Gartner, A
    [J]. CURRENT BIOLOGY, 2001, 11 (24) : 1934 - 1944
  • [3] Mrc1 transduces signals of DNA replication stress to activate Rad53
    Alcasabas, AA
    Osborn, AJ
    Bachant, J
    Hu, FH
    Werler, PJH
    Bousset, K
    Furuya, K
    Diffley, JFX
    Carr, AM
    Elledge, SJ
    [J]. NATURE CELL BIOLOGY, 2001, 3 (11) : 958 - 965
  • [4] Brachmann CB, 1998, YEAST, V14, P115
  • [5] HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability
    Collis, Spencer J.
    Barber, Louise J.
    Clark, Allison J.
    Martin, Julie S.
    Ward, Jordan D.
    Boulton, Simon J.
    [J]. NATURE CELL BIOLOGY, 2007, 9 (04) : 391 - U62
  • [6] The yeast Xrs2 complex functions in S phase checkpoint regulation
    D'Amours, D
    Jackson, SP
    [J]. GENES & DEVELOPMENT, 2001, 15 (17) : 2238 - 2249
  • [7] Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
    Falck, J
    Coates, J
    Jackson, SP
    [J]. NATURE, 2005, 434 (7033) : 605 - 611
  • [8] Fortuna M, 2001, CURRENT PROTOCOLS CY
  • [9] Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans
    Garcia-Muse, T
    Boulton, SJ
    [J]. EMBO JOURNAL, 2005, 24 (24) : 4345 - 4355
  • [10] A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans
    Gartner, A
    Milstein, S
    Ahmed, S
    Hodgkin, J
    Hengartner, MO
    [J]. MOLECULAR CELL, 2000, 5 (03) : 435 - 443