of Work: DNA damage produces cell death or mutation, both of which can have serious health consequences. Most DNA damage is repaired before it can cause harm. The classically defined mechanisms of repair are direct reversal of the damage, excision of the damage followed by resynthesis of the damaged strand, recombinational processes that bypass the damage without removing it, and mutagenic translesion synthesis. A fourth but poorly characterized mechanism has been identified in bacteriophage T4. Mutations in genes of DNA replication reduce survival after treatments inducing a variety of kinds of damage, but do not otherwise appreciably affect phage reproduction. The process appears not to involve any of the classical mechanisms. We will investigate the processing of damaged DNA in vitro using wild-type and mutant enzymes, and will seek additional mutations in the epistasis group.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES061055-01
Application #
6106739
Study Section
Special Emphasis Panel (LMG)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Schultz Jr, Gary E; Drake, John W (2008) Templated mutagenesis in bacteriophage T4 involving imperfect direct or indirect sequence repeats. Genetics 178:661-73
Schultz Jr, Gary E; Carver, Geraldine T; Drake, John W (2006) A role for replication repair in the genesis of templated mutations. J Mol Biol 358:963-73
Kadyrov, Farid A; Drake, John W (2004) UvsX recombinase and Dda helicase rescue stalled bacteriophage T4 DNA replication forks in vitro. J Biol Chem 279:35735-40
Kadyrov, Farid A; Drake, John W (2003) Properties of bacteriophage T4 proteins deficient in replication repair. J Biol Chem 278:25247-55
Kadyrov, Farid A; Drake, John W (2002) Characterization of DNA synthesis catalyzed by bacteriophage T4 replication complexes reconstituted on synthetic circular substrates. Nucleic Acids Res 30:4387-97
Kadyrov, F A; Drake, J W (2001) Conditional coupling of leading-strand and lagging-strand DNA synthesis at bacteriophage T4 replication forks. J Biol Chem 276:29559-66