In eucaryotes if chromosomes are damaged, the cell cycle arrests in G2, just before mitosis and chromosome segregation. Genomic stability and viability of eucaryotes requires controls that ensure mitosis does not occur until chromosomes are intact. Arrest in G2 after DNA damage is genetically regulated. The long-term objective of my research is to understand how the cell detects DNA damage and signals arrest of the cell cycle. In Saccharomyces cerevisiae, the mechanism of arrest in G2 requires a negative regulator, the RAD9 gene. The genetic pathway controlling arrest in G2 is complex; genetic analysis of mutants defective for arrest in G2 show that 6 genes are essential for this regulatory control. My research focuses on determining how the 6 genes for mitosis-entry checkpoint, control cell cycle arrest after DNA damage. The MEC genes will be isolated and their DNA sequences determined to see it they encode proteins of known biochemical or structural function. (DNA sequence for two MEC genes has been completed). Genetic controls of mitosis by the MEC genes may be complex and involve regulation of precesses in addition to arrest in G2 after DNA damage; mec mutants will be examined for a constitutive role in the transition from G2 to mitosis, for control of DNA repair, and for regulation of arrest in other phases of the cell cycle in addition to G2. Using the isolated MEC genes two genetic approaches will examine epistasis and physical interactions of gene products; a description of hierarchy of the MEC genetic pathway will emerge. Additional MEC loci will be identified using a new genetic selection, with a focus on genes that may be essential for mitosis and the target of MEC-dependent control. Finally, the roles of three genes known to be essential, or to regulate, mitosis will be tested genetically for roles as possible targets or mediators of MEC-dependent negative control (including CDC28, MIH1, and wee1).

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetics Study Section (GEN)
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University of Arizona
Schools of Arts and Sciences
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Admire, Anthony; Shanks, Lisa; Danzl, Nicole et al. (2006) Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast. Genes Dev 20:159-73
Weinert, T; Little, E; Shanks, L et al. (2000) Details and concerns regarding the G2/M DNA damage checkpoint in budding yeast. Cold Spring Harb Symp Quant Biol 65:433-41
Gardner, R; Putnam, C W; Weinert, T (1999) RAD53, DUN1 and PDS1 define two parallel G2/M checkpoint pathways in budding yeast. EMBO J 18:3173-85
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Lydall, D; Weinert, T (1997) G2/M checkpoint genes of Saccharomyces cerevisiae: further evidence for roles in DNA replication and/or repair. Mol Gen Genet 256:638-51
Kiser, G L; Weinert, T A (1996) Distinct roles of yeast MEC and RAD checkpoint genes in transcriptional induction after DNA damage and implications for function. Mol Biol Cell 7:703-18
Lydall, D; Weinert, T (1995) Yeast checkpoint genes in DNA damage processing: implications for repair and arrest. Science 270:1488-91
Kiser, G L; Weinert, T A (1995) GUF1, a gene encoding a novel evolutionarily conserved GTPase in budding yeast. Yeast 11:1311-6
Weinert, T A; Kiser, G L; Hartwell, L H (1994) Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 8:652-65

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