Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair Journal Article

  

Authors:	Sinha, K. M.; Stephanou, N. C.; Gao, F.; Glickman, M. S.; Shuman, S.
Article Title:	Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repair
Abstract:	Mycobacterium tuberculosis and other bacterial pathogens have a Ku-dependent nonhomologous end joining pathway of DNA double-strand break repair. Here we identify mycobacterial UvrD1 as a novel interaction partner for Ku in a genome-wide yeast two-hybrid screen. UvrD1 per se is a vigorous DNA-dependent ATPase but a feeble DNA helicase. Ku stimulates UvrD1 to catalyze ATP-dependent unwinding of 3′-tailed DNAs. UvrD1, Ku, and DNA form a stable ternary complex in the absence of ATP. The Ku binding determinants are located in the distinctive C-terminal segment of UvrD1. A second mycobacterial paralog, UvrD2, is a vigorous Ku-independent DNA helicase. Ablation of UvrD1 sensitizes Mycobacterium smegmatis to killing by ultraviolet and ionizing radiation and to a single chromosomal break generated by I-SceI endonuclease. The physical and functional interactions of bacterial Ku and UvrD1 highlight the potential for cross-talk between components of nonhomologous end joining and nucleotide excision repair pathways. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
Keywords:	unclassified drug; genetics; nonhuman; protein function; ultraviolet radiation; metabolism; dna repair; carboxy terminal sequence; protein binding; protein interaction; enzymology; enzyme activity; bacteria (microorganisms); radiation exposure; physiology; dna strand breakage; bacterial protein; mycobacterium tuberculosis; bacterial proteins; double stranded dna; pathogens; ionizing radiation; dna breaks, double-stranded; chromosome breakage; double stranded dna break; dna structure; excision repair; protein structure, tertiary; binding sites; molecular interaction; helicase; catalysis; adenosine triphosphate; endonuclease; ku antigen; ultraviolet rays; protein tertiary structure; dna helicases; dna helicase; chromosomes; dna sequences; complexation; mycobacterium smegmatis; bacteria; hybrid gene; ablation; gamma radiation; gamma rays; kurchatovium; endodeoxyribonuclease scei; type ii site specific deoxyribonuclease; deoxyribonucleases, type ii site-specific; paralogy; chromosomal break; dna double strand break repair; mycobacterial uvrd1; ternary alloys; uvrd1 protein; uvrd2 protein
Journal Title:	Journal of Biological Chemistry
Volume:	282
Issue:	20
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Date Published:	2007-05-18
Start Page:	15114
End Page:	15125
Language:	English
DOI:	10.1074/jbc.M701167200
PUBMED:	17376770
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-34447515950&partnerID=40&md5=62a267b38a6cd45ba669db908acd942b
Notes:	--- - "Cited By (since 1996): 20" - "Export Date: 17 November 2011" - "CODEN: JBCHA" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/18294