Abstract

Mismatch repair is an error avoidance pathway devoted to enhancing the fidelity of DNA replication and maintaining genetic stability. Mutations in mismatch repair genes predispose individuals to cancer. The 8-oxoG lesion is a major stable product of oxidative damage, has the most deleterious effects, and is a substrate for the E. coli Mut Y protein. The functional groups of the Mut Y protein for substrate specificity and catalysis will be defined. This will be achieved by site-directed mutagenesis of the mut Y gene and construction of chimeric proteins of Mut Y and GTMR. The functional roles of the C-terminal domain of Mut Y will also be elucidated. The structure of the 15 kDa terminal fragment will be determined by NMR. Possible interactions between Mut Y and Mut M will be investigated. Purified SpMYH protein of fission yeast will be assayed on DNA containing mismatches. The effects of overexpression of SpMYH in E. coli and yeast will be investigated. Yeast mutants defective in myh will be constructed and their mutation rates will be measured.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM035132-14
Application #
2900610
Study Section
Special Emphasis Panel (ZRG5-BM-1 (02))
Project Start
1985-07-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
14
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Biochemistry
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Jin, Jin; Hwang, Bor-Jang; Chang, Po-Wen et al. (2014) Interaction of apurinic/apyrimidinic endonuclease 2 (Apn2) with Myh1 DNA glycosylase in fission yeast. DNA Repair (Amst) 15:1-10
Chang, Dau-Yin; Shi, Guoli; Durand-Dubief, Mickael et al. (2011) The role of MutY homolog (Myh1) in controlling the histone deacetylase Hst4 in the fission yeast Schizosaccharomyces pombe. J Mol Biol 405:653-65
Luncsford, Paz J; Chang, Dau-Yin; Shi, Guoli et al. (2010) A structural hinge in eukaryotic MutY homologues mediates catalytic activity and Rad9-Rad1-Hus1 checkpoint complex interactions. J Mol Biol 403:351-70
Chang, Po-Wen; Madabushi, Amrita; Lu, A-Lien (2009) Insights into the role of Val45 and Gln182 of Escherichia coli MutY in DNA substrate binding and specificity. BMC Biochem 10:19
Bai, Haibo; Lu, A-Lien (2007) Physical and functional interactions between Escherichia coli MutY glycosylase and mismatch repair protein MutS. J Bacteriol 189:902-10
Lu, A-Lien; Bai, Haibo; Shi, Guoli et al. (2006) MutY and MutY homologs (MYH) in genome maintenance. Front Biosci 11:3062-80
Lu-Chang, A-Lien (2006) Isolation and analyses of MutY homologs (MYH). Methods Enzymol 408:64-78
Shi, Guoli; Chang, Dau-Yin; Cheng, Chih-Chien et al. (2006) Physical and functional interactions between MutY glycosylase homologue (MYH) and checkpoint proteins Rad9-Rad1-Hus1. Biochem J 400:53-62
Lu, A-Lien; Lee, Chih-Yung; Li, Lina et al. (2006) Physical and functional interactions between Escherichia coli MutY and endonuclease VIII. Biochem J 393:381-7
Chang, Dau-Yin; Lu, A-Lien (2005) Interaction of checkpoint proteins Hus1/Rad1/Rad9 with DNA base excision repair enzyme MutY homolog in fission yeast, Schizosaccharomyces pombe. J Biol Chem 280:408-17

Showing the most recent 10 out of 40 publications