Abstract

This is a proposal to investigate chromatin assembly factors in yeast, using complementary genetic and biochemical approaches. The PI will focus on a yeast protein complex termed Chromatin Assembly Factor-I (CAF-I) that assembles histones H3 and H4 preferentially onto replicated DNA in vitro. Cells containing null alleles of the genes encoding CAF-I subunits are viable but display altered sensitivity to hydroxyurea and benomyl, drugs that disrupt the cell cycle. The PI will test these mutants for defects in chromatin structure, gene expression, and cell cycle checkpoint control. To determine if redundant assembly activities account for the survival of cells lacking CAF-I, the PI will screen for mutations that generate a requirement for intact CAF-I and for high copy suppressors of the drug sensitivity phenotypes of CAF-I mutants. Epitope-tagged yeast CAF-I subunits will be used to isolate proteins bound to CAF-I in vivo. Proteins identified by these methods will be tested in biochemical assays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055712-05
Application #
6386683
Study Section
Molecular Cytology Study Section (CTY)
Program Officer
Carter, Anthony D
Project Start
1997-06-01
Project End
2002-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
5
Fiscal Year
2001
Total Cost
$271,722
Indirect Cost

  Institution

Name
Lawrence Berkeley National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720

  Publications

Sun, Xiaoming; Bizhanova, Aizhan; Matheson, Timothy D et al. (2017) Ki-67 Contributes to Normal Cell Cycle Progression and Inactive X Heterochromatin in p21 Checkpoint-Proficient Human Cells. Mol Cell Biol 37:
Matheson, Timothy D; Kaufman, Paul D (2017) The p150N domain of chromatin assembly factor-1 regulates Ki-67 accumulation on the mitotic perichromosomal layer. Mol Biol Cell 28:21-29
Matheson, Timothy D; Kaufman, Paul D (2016) Grabbing the genome by the NADs. Chromosoma 125:361-71
Kaufman, Paul D (2015) Want reprogramming? Cut back on the chromatin assembly! Nat Struct Mol Biol 22:648-50
Lopes da Rosa, Jessica; Bajaj, Vineeta; Spoonamore, James et al. (2013) A small molecule inhibitor of fungal histone acetyltransferase Rtt109. Bioorg Med Chem Lett 23:2853-9
Lopes da Rosa, Jessica; Holik, John; Green, Erin M et al. (2011) Overlapping regulation of CenH3 localization and histone H3 turnover by CAF-1 and HIR proteins in Saccharomyces cerevisiae. Genetics 187:9-19
Kaufman, Paul D (2011) New partners for HP1 in transcriptional gene silencing. Mol Cell 41:1-2
Lopes da Rosa, Jessica; Boyartchuk, Victor L; Zhu, Lihua Julie et al. (2010) Histone acetyltransferase Rtt109 is required for Candida albicans pathogenesis. Proc Natl Acad Sci U S A 107:1594-9
Kaufman, Paul D (2010) Toxicity and lifespan extension: complex outcomes of histone overexpression in budding yeast. Cell Cycle 9:4611-2
Kaufman, Paul D; Rando, Oliver J (2010) Chromatin as a potential carrier of heritable information. Curr Opin Cell Biol 22:284-90

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