EXCEED THE SPACE PROVIDED. Equal segregation of chromosomes to opposite poles during mitosis is essential for cell viability. To accomplish this chromosomes are condensed and attached to spindle microtubules at the centromere which coordinates the separation of sister chromatids at anaphase. Missegregation of chromosomes has been associated with many human diseases including several congenital disorders and nearly all forms of cancer. To better understand how chromosome segregation occurs we have begun to study the centromere in the free-living soil nematode C. elegans. The centromere in C. elegans is approximately 10 times larger than it is in human cells making this system more amenable to cell biological studies. In addition functional studies can be carried out rapidly because it has recently become possible to eliminate gene functions using RNA mediated interference. My goal is to identify the proteins involved in the assembly of the centromere / kinetochore and to identify the mechanisms involved in forming new centromeres. The approaches I will use are a combination of biochemical and cytological studies using RNAi and temperature sensitive mutants affected in these processes. PERFORMANCE SITE ========================================Section End===========================================

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Carter, Anthony D
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Fred Hutchinson Cancer Research Center
United States
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Budde, Mark W; Roth, Mark B (2010) Hydrogen sulfide increases hypoxia-inducible factor-1 activity independently of von Hippel-Lindau tumor suppressor-1 in C. elegans. Mol Biol Cell 21:212-7
Chan, Kin; Goldmark, Jesse P; Roth, Mark B (2010) Suspended animation extends survival limits of Caenorhabditis elegans and Saccharomyces cerevisiae at low temperature. Mol Biol Cell 21:2161-71
Miller, Dana L; Roth, Mark B (2009) C. elegans are protected from lethal hypoxia by an embryonic diapause. Curr Biol 19:1233-7
Frazier 3rd, Harold N; Roth, Mark B (2009) Adaptive sugar provisioning controls survival of C. elegans embryos in adverse environments. Curr Biol 19:859-63
Chan, Kin; Roth, Mark B (2008) Anoxia-induced suspended animation in budding yeast as an experimental paradigm for studying oxygen-regulated gene expression. Eukaryot Cell 7:1795-808
Miller, Dana L; Roth, Mark B (2007) Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci U S A 104:20618-22
Moore, Landon L; Stanvitch, Gerald; Roth, Mark B et al. (2005) HCP-4/CENP-C promotes the prophase timing of centromere resolution by enabling the centromere association of HCP-6 in Caenorhabditis elegans. Mol Cell Biol 25:2583-92
Blackstone, Eric; Morrison, Mike; Roth, Mark B (2005) H2S induces a suspended animation-like state in mice. Science 308:518
Nystul, Todd G; Roth, Mark B (2004) Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 101:9133-6
Stear, Jeffrey H; Roth, Mark B (2004) The Caenorhabditis elegans kinetochore reorganizes at prometaphase and in response to checkpoint stimuli. Mol Biol Cell 15:5187-96

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