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.
| 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 |
