DNA Restriction, Damage and Repair

Linn, Stuart M.

Abstract

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.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of General Medical Sciences (NIGMS)
• Type: Research Project (R01)
• Project #: 2R01GM019020-19
• Application #: 3563671
• Study Section: Microbial Physiology and Genetics Subcommittee 2 (MBC)
• Project Start: 1977-01-01
• Project End: 1991-12-31
• Budget Start: 1987-01-01
• Budget End: 1987-12-31
• Support Year: 19
• Fiscal Year: 1987

Institution

• Name: University of California Berkeley
• DUNS #: 094878337
• City: Berkeley
• State: CA
• Country: United States
• Zip Code: 94704

Publications

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

Rai, Priyamvada; Wemmer, David E; Linn, Stuart (2005) Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences. Nucleic Acids Res 33:497-510

Brumaghim, Julia L; Li, Ying; Henle, Ernst et al. (2003) Effects of hydrogen peroxide upon nicotinamide nucleotide metabolism in Escherichia coli: changes in enzyme levels and nicotinamide nucleotide pools and studies of the oxidation of NAD(P)H by Fe(III). J Biol Chem 278:42495-504

Rai, Priyamvada; Cole, Timothy David; Thompson, Elizabeth et al. (2003) Steady-state and time-resolved fluorescence studies indicate an unusual conformation of 2-aminopurine within ATAT and TATA duplex DNA sequences. Nucleic Acids Res 31:2323-32

Rai, P; Cole, T D; Wemmer, D E et al. (2001) Localization of Fe(2+) at an RTGR sequence within a DNA duplex explains preferential cleavage by Fe(2+) and H2O2. J Mol Biol 312:1089-101

Linn, S (1998) DNA damage by iron and hydrogen peroxide in vitro and in vivo. Drug Metab Rev 30:313-26