![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Research Papers
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721.
Abstract
In eukaryotes a cell-cycle control termed a checkpoint causes arrest in the S or G2 phases when chromosomes are incompletely replicated or damaged. Previously, we showed in budding yeast that RAD9 and RAD17 are checkpoint genes required for arrest in the G2 phase after DNA damage. Here, we describe a genetic strategy that identified four additional checkpoint genes that act in two pathways. Both classes of genes are required for arrest in the G2 phase after DNA damage, and one class of genes is also required for arrest in S phase when DNA replication is incomplete. The G2-specific genes include MEC3 (for mitosis entry checkpoint), RAD9, RAD17, and RAD24. The genes common to both S phase and G2 phase pathways are MEC1 and MEC2. The MEC2 gene proves to be identical to the RAD53 gene. Checkpoint mutants were identified by their interactions with a temperature-sensitive allele of the cell division cycle gene CDC13; cdc13 mutants arrested in G2 and survived at the restrictive temperature, whereas all cdc13 checkpoint double mutants failed to arrest in G2 and died rapidly at the restrictive temperature. The cell-cycle roles of the RAD and MEC genes were examined by combination of rad and mec mutant alleles with 10 cdc mutant alleles that arrest in different stages of the cell cycle at the restrictive temperature and by the response of rad and mec mutant alleles to DNA damaging agents and to hydroxyurea, a drug that inhibits DNA replication. We conclude that the checkpoint in budding yeast consists of overlapping S-phase and G2-phase pathways that respond to incomplete DNA replication and/or DNA damage and cause arret of cells before mitosis.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Baldo, V. Testoni, G. Lucchini, and M. P. Longhese Dominant TEL1-hy Mutations Compensate for Mec1 Lack of Functions in the DNA Damage Response Mol. Cell. Biol., January 1, 2008; 28(1): 358 - 375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Roberts, I. W. Zaidi, J. A. Vaisica, M. Peter, and G. W. Brown Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase Mol. Biol. Cell, January 1, 2008; 19(1): 171 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. KUNDAJE, S. LIANOGLOU, X. LI, D. QUIGLEY, M. ARIAS, C. H. WIGGINS, L. ZHANG, and C. LESLIE Learning Regulatory Programs That Accurately Predict Differential Expression with MEDUSA Ann. N.Y. Acad. Sci., December 1, 2007; 1115(1): 178 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Theis, A. Dershowitz, C. Irene, C. Maciariello, M. L. Tobin, G. Liberi, S. Tabrizifard, M. Korus, L. Fabiani, and C. S. Newlon Identification of Mutations That Decrease the Stability of a Fragment of Saccharomyces cerevisiae Chromosome III Lacking Efficient Replicators Genetics, November 1, 2007; 177(3): 1445 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Alvino, D. Collingwood, J. M. Murphy, J. Delrow, B. J. Brewer, and M. K. Raghuraman Replication in Hydroxyurea: It's a Matter of Time Mol. Cell. Biol., September 15, 2007; 27(18): 6396 - 6406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Yong-Gonzalez, B.-D. Wang, P. Butylin, I. Ouspenski, and A. Strunnikov Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids Genes Cells, September 1, 2007; 12(9): 1075 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ma, J. McQueen, L. Cuschieri, J. Vogel, and V. Measday Spc24 and Stu2 Promote Spindle Integrity When DNA Replication Is Stalled Mol. Biol. Cell, August 1, 2007; 18(8): 2805 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Liang and Y. Wang DNA Damage Checkpoints Inhibit Mitotic Exit by Two Different Mechanisms Mol. Cell. Biol., July 15, 2007; 27(14): 5067 - 5078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Torres-Rosell, G. De Piccoli, V. Cordon-Preciado, S. Farmer, A. Jarmuz, F. Machin, P. Pasero, M. Lisby, J. E. Haber, and L. Aragon Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses Science, March 9, 2007; 315(5817): 1411 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Oeffinger, A. Fatica, M. P. Rout, and D. Tollervey Yeast Rrp14p is required for ribosomal subunit synthesis and for correct positioning of the mitotic spindle during mitosis Nucleic Acids Res., February 28, 2007; 35(4): 1354 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. Dohrmann and R. A. Sclafani Novel Role for Checkpoint Rad53 Protein Kinase in the Initiation of Chromosomal DNA Replication in Saccharomyces cerevisiae Genetics, September 1, 2006; 174(1): 87 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Kastenmayer, L. Ni, A. Chu, L. E. Kitchen, W.-C. Au, H. Yang, C. D. Carter, D. Wheeler, R. W. Davis, J. D. Boeke, et al. Functional genomics of genes with small open reading frames (sORFs) in S. cerevisiae. Genome Res., March 1, 2006; 16(3): 365 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Venkatesan, J. J. Hsu, N. A. Lawrence, B. D. Preston, and L. A. Loeb Mutator Phenotypes Caused by Substitution at a Conserved Motif A Residue in Eukaryotic DNA Polymerase {delta} J. Biol. Chem., February 17, 2006; 281(7): 4486 - 4494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Bartrand, D. Iyasu, S. M. Marinco, and G. S. Brush Evidence of Meiotic Crossover Control in Saccharomyces cerevisiae Through Mec1-Mediated Phosphorylation of Replication Protein A Genetics, January 1, 2006; 172(1): 27 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Cobb, T. Schleker, V. Rojas, L. Bjergbaek, J. A. Tercero, and S. M. Gasser Replisome instability, fork collapse, and gross chromosomal rearrangements arise synergistically from Mec1 kinase and RecQ helicase mutations Genes & Dev., December 15, 2005; 19(24): 3055 - 3069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Carter, L. E. Kitchen, W.-C. Au, C. M. Babic, and M. A. Basrai Loss of SOD1 and LYS7 Sensitizes Saccharomyces cerevisiae to Hydroxyurea and DNA Damage Agents and Downregulates MEC1 Pathway Effectors Mol. Cell. Biol., December 1, 2005; 25(23): 10273 - 10285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Corda, S. E. Lee, S. Guillot, A. Walther, J. Sollier, A. Arbel-Eden, J. E. Haber, and V. Geli Inactivation of Ku-Mediated End Joining Suppresses mec1{Delta} Lethality by Depleting the Ribonucleotide Reductase Inhibitor Sml1 through a Pathway Controlled by Tel1 Kinase and the Mre11 Complex Mol. Cell. Biol., December 1, 2005; 25(23): 10652 - 10664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Baumgartner and V. Lundblad Telomere identity crisis Genes & Dev., November 1, 2005; 19(21): 2522 - 2525. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sharp, G. Rizki, and P. D. Kaufman Regulation of Histone Deposition Proteins Asf1/Hir1 by Multiple DNA Damage Checkpoint Kinases in Saccharomyces cerevisiae Genetics, November 1, 2005; 171(3): 885 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wysocki, A. Javaheri, S. Allard, F. Sha, J. Cote, and S. J. Kron Role of Dot1-Dependent Histone H3 Methylation in G1 and S Phase DNA Damage Checkpoint Functions of Rad9 Mol. Cell. Biol., October 1, 2005; 25(19): 8430 - 8443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Guo, L. L. Breeden, H. Zarbl, B. D. Preston, and D. L. Eaton Expression of a Human Cytochrome P450 in Yeast Permits Analysis of Pathways for Response to and Repair of Aflatoxin-Induced DNA Damage Mol. Cell. Biol., July 15, 2005; 25(14): 5823 - 5833. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Alpha-Bazin, A. Lorphelin, N. Nozerand, G. Charier, C. Marchetti, F. Berenguer, J. Couprie, B. Gilquin, S. Zinn-Justin, and E. Quemeneur Boundaries and physical characterization of a new domain shared between mammalian 53BP1 and yeast Rad9 checkpoint proteins Protein Sci., July 1, 2005; 14(7): 1827 - 1839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Karumbati and T. E. Wilson Abrogation of the Chk1-Pds1 Checkpoint Leads to Tolerance of Persistent Single-Strand Breaks in Saccharomyces cerevisiae Genetics, April 1, 2005; 169(4): 1833 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bachant, S. R. Jessen, S. E. Kavanaugh, and C. S. Fielding The yeast S phase checkpoint enables replicating chromosomes to bi-orient and restrain spindle extension during S phase distress J. Cell Biol., March 28, 2005; 168(7): 999 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Mallory, G. Crudden, B. L. Johnson, C. Mo, C. A. Pierson, M. Bard, and R. J. Craven Dap1p, a Heme-Binding Protein That Regulates the Cytochrome P450 Protein Erg11p/Cyp51p in Saccharomyces cerevisiae Mol. Cell. Biol., March 1, 2005; 25(5): 1669 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Saiardi, A. C. Resnick, A. M. Snowman, B. Wendland, and S. H. Snyder From the Cover: Inositol pyrophosphates regulate cell death and telomere length through phosphoinositide 3-kinase-related protein kinases PNAS, February 8, 2005; 102(6): 1911 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dunaway, H.-Y. Liu, and N. C. Walworth Interaction of 14-3-3 protein with Chk1 affects localization and checkpoint function J. Cell Sci., January 1, 2005; 118(1): 39 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Green and J. J. Li Loss of Rereplication Control in Saccharomyces cerevisiae Results in Extensive DNA Damage Mol. Biol. Cell, January 1, 2005; 16(1): 421 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Clerici, V. Baldo, D. Mantiero, F. Lottersberger, G. Lucchini, and M. P. Longhese A Tel1/MRX-Dependent Checkpoint Inhibits the Metaphase-to-Anaphase Transition after UV Irradiation in the Absence of Mec1 Mol. Cell. Biol., December 1, 2004; 24(23): 10126 - 10144. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Ramey, S. Howar, M. Adkins, J. Linger, J. Spicer, and J. K. Tyler Activation of the DNA Damage Checkpoint in Yeast Lacking the Histone Chaperone Anti-Silencing Function 1 Mol. Cell. Biol., December 1, 2004; 24(23): 10313 - 10327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Luciani, M. Oehlmann, and J. J. Blow Characterization of a novel ATR-dependent, Chk1-independent, intra-S-phase checkpoint that suppresses initiation of replication in Xenopus J. Cell Sci., December 1, 2004; 117(25): 6019 - 6030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shapira, E. Segal, and D. Botstein Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress Mol. Biol. Cell, December 1, 2004; 15(12): 5659 - 5669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Myung, S. Smith, and R. D. Kolodner Mitotic checkpoint function in the formation of gross chromosomal rearrangements in Saccharomyces cerevisiae PNAS, November 9, 2004; 101(45): 15980 - 15985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hu, D. S. Roos, S. O. Angel, and J. M. Murray Variability and heritability of cell division pathways in Toxoplasma gondii J. Cell Sci., November 1, 2004; 117(23): 5697 - 5705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Pike, N. Tenis, and J. Heierhorst Rad53 Kinase Activation-independent Replication Checkpoint Function of the N-terminal Forkhead-associated (FHA1) Domain J. Biol. Chem., September 17, 2004; 279(38): 39636 - 39644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Schollaert, J. M. Poisson, J. S. Searle, J. A. Schwanekamp, C. R. Tomlinson, and Y. Sanchez A Role for Saccharomyces cerevisiae Chk1p in the Response to Replication Blocks Mol. Biol. Cell, September 1, 2004; 15(9): 4051 - 4063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Bartrand, D. Iyasu, and G. S. Brush DNA Stimulates Mec1-mediated Phosphorylation of Replication Protein A J. Biol. Chem., June 18, 2004; 279(25): 26762 - 26767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Matsui, Y. Katsuno, T. Inoue, F. Fujita, T. Joh, H. Niida, H. Murakami, M. Itoh, and M. Nakanishi Negative Regulation of Chk2 Expression by p53 Is Dependent on the CCAAT-binding Transcription Factor NF-Y J. Biol. Chem., June 11, 2004; 279(24): 25093 - 25100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Baroni, V. Viscardi, H. Cartagena-Lirola, G. Lucchini, and M. P. Longhese The Functions of Budding Yeast Sae2 in the DNA Damage Response Require Mec1- and Tel1-Dependent Phosphorylation Mol. Cell. Biol., May 15, 2004; 24(10): 4151 - 4165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bergkessel and J. C. Reese An Essential Role for the Saccharomyces cerevisiae DEAD-Box Helicase DHH1 in G1/S DNA-Damage Checkpoint Recovery Genetics, May 1, 2004; 167(1): 21 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Culligan, A. Tissier, and A. Britt ATR Regulates a G2-Phase Cell-Cycle Checkpoint in Arabidopsis thaliana PLANT CELL, May 1, 2004; 16(5): 1091 - 1104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Armbruster, C. M. Linardic, T. Veldman, N. P. Bansal, D. L. Downie, and C. M. Counter Rescue of an hTERT Mutant Defective in Telomere Elongation by Fusion with hPot1 Mol. Cell. Biol., April 15, 2004; 24(8): 3552 - 3561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Pike, S. Yongkiettrakul, M.-D. Tsai, and J. Heierhorst Mdt1, a Novel Rad53 FHA1 Domain-Interacting Protein, Modulates DNA Damage Tolerance and G2/M Cell Cycle Progression in Saccharomyces cerevisiae Mol. Cell. Biol., April 1, 2004; 24(7): 2779 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Clifford, S. M. Marinco, and G. S. Brush The Meiosis-specific Protein Kinase Ime2 Directs Phosphorylation of Replication Protein A J. Biol. Chem., February 13, 2004; 279(7): 6163 - 6170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T. Blankley and D. Lydall A domain of Rad9 specifically required for activation of Chk1 in budding yeast J. Cell Sci., February 1, 2004; 117(4): 601 - 608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lottersberger, F. Rubert, V. Baldo, G. Lucchini, and M. P. Longhese Functions of Saccharomyces cerevisiae 14-3-3 Proteins in Response to DNA Damage and to DNA Replication Stress Genetics, December 1, 2003; 165(4): 1717 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. W. Jiang and C. M. Kang Induction of S. cerevisiae Filamentous Differentiation by Slowed DNA Synthesis Involves Mec1, Rad53 and Swe1 Checkpoint Proteins Mol. Biol. Cell, December 1, 2003; 14(12): 5116 - 5124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ben-Aroya, A. Koren, B. Liefshitz, R. Steinlauf, and M. Kupiec ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C PNAS, August 19, 2003; 100(17): 9906 - 9911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Osborn and S. J. Elledge Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53 Genes & Dev., July 15, 2003; 17(14): 1755 - 1767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Scott and S. E. Plon Loss of Sin3/Rpd3 Histone Deacetylase Restores the DNA Damage Response in Checkpoint-Deficient Strains of Saccharomyces cerevisiae Mol. Cell. Biol., July 1, 2003; 23(13): 4522 - 4531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Michel, J. F. McCarville, and Y. Xiong A Role for Saccharomyces cerevisiae Cul8 Ubiquitin Ligase in Proper Anaphase Progression J. Biol. Chem., June 13, 2003; 278(25): 22828 - 22837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Grandin and M. Charbonneau The Rad51 Pathway of Telomerase-Independent Maintenance of Telomeres Can Amplify TG1-3 Sequences in yku and cdc13 Mutants of Saccharomyces cerevisiae Mol. Cell. Biol., June 1, 2003; 23(11): 3721 - 3734. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Hand, N. Jia, M. Bard, and R. J. Craven Saccharomyces cerevisiae Dap1p, a Novel DNA Damage Response Protein Related to the Mammalian Membrane-Associated Progesterone Receptor Eukaryot. Cell, April 1, 2003; 2(2): 306 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Zewail, M. W. Xie, Y. Xing, L. Lin, P. F. Zhang, W. Zou, J. P. Saxe, and J. Huang Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin PNAS, March 18, 2003; 100(6): 3345 - 3350. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Chiroli, R. Fraschini, A. Beretta, M. Tonelli, G. Lucchini, and S. Piatti Budding yeast PAK kinases regulate mitotic exit by two different mechanisms J. Cell Biol., March 17, 2003; 160(6): 857 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Brown and D. Baltimore Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance Genes & Dev., March 1, 2003; 17(5): 615 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Chang, M. Bellaoui, C. Boone, and G. W. Brown A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage PNAS, December 24, 2002; 99(26): 16934 - 16939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shimada, P. Pasero, and S. M. Gasser ORC and the intra-S-phase checkpoint: a threshold regulates Rad53p activation in S phase Genes & Dev., December 15, 2002; 16(24): 3236 - 3252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
