The long-term objectives of this project are to understand several aspects of how the genetic integrity of a cell is maintained on the one hand or methodically altered on the other. Microbial systems are being utilized as they provide a genetic base for validating the significance and complementing of biochemical observations. Specifically, this proposal outlines biochemical and genetic studies of: (1) the mechanism by which the Type I restriction enzyme, EcoB, inactivates DNA; (2) the movement of the recBC DNase along DNA; (3) the mechanisms by which H202 damages DNA and how such DNA damage is avoided and/or repaired; (4) the mechanisms of several DNA repair enzymes - E. coli endonucleases III, IV and V and exonuclease III and phage T4 endonuclease; (5) the genesis and significance of a form of DNA polymerase I, pol I*, which appears after SOS induction. These studies ultimately will provide a framework for studying related mammalian systems so as ultimately to be able to understand how a human cell maintains its genetic integrity and avoids many diseased states related to abnormal DNA metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM019020-25
Application #
3484284
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-01-01
Project End
1996-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
25
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Chattopadhyaya, Rajagopal (2014) Oxidative damage to DNA constituents by iron-mediated Fenton reactions--the thymidine family. J Biomol Struct Dyn 32:155-69
Chattopadhyaya, Rajagopal; Goswami, Bhaswati (2012) Oxidative damage to DNA constituents by iron-mediated Fenton reactions: the deoxyadenosine family. J Biomol Struct Dyn 30:394-406
Henle, E S; Han, Z; Tang, N et al. (1999) Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. J Biol Chem 274:962-71
Luo, Y; Henle, E S; Chatopadhyaya, R et al. (1994) Detecting DNA damage caused by iron and hydrogen peroxide. Methods Enzymol 234:51-9
Luo, Y; Han, Z; Chin, S M et al. (1994) Three chemically distinct types of oxidants formed by iron-mediated Fenton reactions in the presence of DNA. Proc Natl Acad Sci U S A 91:12438-42