The overall goal of this research proposal is to reveal the molecular function of RecN, a protein critical to the repair of DNA double-stranded breaks (DSBs) in bacteria. Bacterial RecN proteins share significant homology to the Structural Maintenance of Chromosomes (SMC) family of proteins. Eukaryotic SMC proteins have essential (although not fully understood) house keeping and tumor suppressor roles in a variety of DNA metabolic processes such as chromosomal condensation, sister chromatid cohesion and recombinational DNA repair. Although extensive genetic evidence underscores the importance of RecN proteins to bacterial genome maintenance, there has been no substantive biochemical investigation into their function and, consequently, the specific reactions requiring RecN have not been identified. This situation reflects the difficulties encountered in working with the Escherichia coli (a model bacterial organism) RecN protein by several research groups due to insolubility of the over-expressed protein. However, we have identified a RecN homolog that is soluble when expressed in E. coli and are positioned to initiate pilot studies to establish testable hypotheses for the biochemical function of bacterial RecN proteins in recombinational DNA repair pathways. This work will provide valuable models for understanding the molecular role that eukaryotic SMC proteins play in genome maintenance.

Public Health Relevance

Biochemical approaches to provide valuable models for understanding the molecular role that SMC proteins play in genome maintenance and recombinational DNA repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Pilot Research Project (SC2)
Project #
5SC2GM083697-03
Application #
8085734
Study Section
Special Emphasis Panel (ZGM1-MBRS-2 (GM))
Program Officer
Janes, Daniel E
Project Start
2009-07-24
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$144,144
Indirect Cost
Name
New Mexico State University Las Cruces
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
173851965
City
Las Cruces
State
NM
Country
United States
Zip Code
88003
Uranga, Lee A; Balise, Victoria D; Benally, Candice V et al. (2011) The Escherichia coli DinD protein modulates RecA activity by inhibiting postsynaptic RecA filaments. J Biol Chem 286:29480-91
Reyes, Emigdio D; Patidar, Praveen L; Uranga, Lee A et al. (2010) RecN is a cohesin-like protein that stimulates intermolecular DNA interactions in vitro. J Biol Chem 285:16521-9