PP2C Phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break

被引:168
作者
Leroy, C
Lee, SE
Vaze, MB
Ochsenbien, F
Guerois, R
Haber, JE
Marsolier-Kergoat, MC [1 ]
机构
[1] CEA Saclay, Serv Biochim & Genet Mol, F-91191 Gif Sur Yvette, France
[2] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA
[3] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA
[4] CEA Saclay, Serv Biophys Fonct Membranaires, F-91191 Gif Sur Yvette, France
关键词
D O I
10.1016/S1097-2765(03)00058-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Saccharomyces cells suffering a DNA double-strand break (DSB) ultimately escape checkpoint-mediated G2/M arrest either by recovery once the lesion is repaired or by adaptation if the lesion proves irreparable. Cells lacking the PP2C-like phosphatases Ptc2 and Ptc3 are unable to adapt to a HO-induced DSB and are also defective in recovering from a repairable DSB. In contrast, overexpression of PTC2 rescues adaptation-defective yku80Delta and cdc5-ad mutants. These effects are not explained by alterations either in the processing of DSB ends or in DSB repair. In vivo and in vitro evidence suggests that phosphorylated forms of Ptc2 and Ptc3 specifically bind to the Rad53 FHA1 domain and inactivate Rad53-dependent pathways during adaptation and recovery by dephosphorylating Rad53.
引用
收藏
页码:827 / 835
页数:9
相关论文
共 37 条
[1]   Chk2 kinase - A busy messenger [J].
Bartek, J ;
Falck, J ;
Lukas, J .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (12) :877-886
[2]   Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity [J].
Bulavin, DV ;
Demidov, ON ;
Saito, S ;
Kauraniemi, P ;
Phillips, C ;
Amundson, SA ;
Ambrosino, C ;
Sauter, G ;
Nebreda, AR ;
Anderson, CW ;
Kallioniemi, A ;
Fornace, AJ ;
Appella, E .
NATURE GENETICS, 2002, 31 (02) :210-215
[3]   The FHA domain is a modular phosphopeptide recognition motif [J].
Durocher, D ;
Henckel, J ;
Fersht, AR ;
Jackson, SP .
MOLECULAR CELL, 1999, 4 (03) :387-394
[4]   The molecular basis of FHA Domain:Phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms [J].
Durocher, D ;
Taylor, IA ;
Sarbassova, D ;
Haire, LF ;
Westcott, SL ;
Jackson, SP ;
Smerdon, SJ ;
Yaffe, MB .
MOLECULAR CELL, 2000, 6 (05) :1169-1182
[5]   Cell cycle checkpoints: Preventing an identity crisis [J].
Elledge, SJ .
SCIENCE, 1996, 274 (5293) :1664-1672
[6]   Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner [J].
Fiscella, M ;
Zhang, HL ;
Fan, SJ ;
Sakaguchi, K ;
Shen, SF ;
Mercer, WE ;
VandeWoude, GF ;
OConnor, PM ;
Appella, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (12) :6048-6053
[7]   FIN13, a novel growth factor-inducible serine-threonine phosphatase which can inhibit cell cycle progression [J].
Guthridge, MA ;
Bellosta, P ;
Tavoloni, N ;
Basilico, C .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (09) :5485-5498
[8]   Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry [J].
Ho, Y ;
Gruhler, A ;
Heilbut, A ;
Bader, GD ;
Moore, L ;
Adams, SL ;
Millar, A ;
Taylor, P ;
Bennett, K ;
Boutilier, K ;
Yang, LY ;
Wolting, C ;
Donaldson, I ;
Schandorff, S ;
Shewnarane, J ;
Vo, M ;
Taggart, J ;
Goudreault, M ;
Muskat, B ;
Alfarano, C ;
Dewar, D ;
Lin, Z ;
Michalickova, K ;
Willems, AR ;
Sassi, H ;
Nielsen, PA ;
Rasmussen, KJ ;
Andersen, JR ;
Johansen, LE ;
Hansen, LH ;
Jespersen, H ;
Podtelejnikov, A ;
Nielsen, E ;
Crawford, J ;
Poulsen, V ;
Sorensen, BD ;
Matthiesen, J ;
Hendrickson, RC ;
Gleeson, F ;
Pawson, T ;
Moran, MF ;
Durocher, D ;
Mann, M ;
Hogue, CWV ;
Figeys, D ;
Tyers, M .
NATURE, 2002, 415 (6868) :180-183
[9]   The Saccharomyces recombination protein Tid1p is required for adaptation from G2/M arrest induced by a double-strand break [J].
Lee, SE ;
Pellicioli, A ;
Malkova, A ;
Foiani, M ;
Haber, JE .
CURRENT BIOLOGY, 2001, 11 (13) :1053-1057
[10]   Saccharomyces Ku70, Mre11/Rad50, and RPA proteins regulate adaptation to G2/M arrest after DNA damage [J].
Lee, SE ;
Moore, JK ;
Holmes, A ;
Umezu, K ;
Kolodner, RD ;
Haber, JE .
CELL, 1998, 94 (03) :399-409