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A distinct physiological role of MutY in mutation prevention in mycobacteria

Kurthkoti, Krishna and Srinath, Thiruneelakantan and Kumar, Pradeep and Malshetty, Vidyasagar S and Sang, Pau Biak and Jain, Ruchi and Manjunath, Ramanathapuram and Varshney, Umesh (2010) A distinct physiological role of MutY in mutation prevention in mycobacteria. In: Microbiology, 156 (Part 1). pp. 88-98.

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Official URL: http://mic.sgmjournals.org/cgi/content/abstract/mi...

Abstract

Oxidative damage to DNA results in the occurrence of 7,8-dihydro-B-oxoguanine (8-oxoG) in the genome. In eubacteria, repair of such damage is initiated by two major base-excision repair enzymes, MutM and MutY. We generated a MutY-deficient strain of Mycobacterium smegmatis to investigate the role of this enzyme in DNA repair. The MutY deficiency in M. smegmatis did not result in either a noteworthy susceptibility to oxidative stress or an increase in the mutation rate. However, rifampicin resistant isolates of the MutY-deficient strain showed distinct mutations in the rifampicin-resistance-determining region of rpoB. Besides the expected C to A (or G to T) mutations, an increase in A to C (or T to G) mutations was also observed. Biochemical characterization of mycobacterial MutY (M. smegmatis and M. tuberculosis) revealed an expected excision of A opposite 8-oxoG in DNA. Additionally, excision of G and T opposite 8-oxoG was detected. MutY formed complexes with DNA containing 8-oxoG: A, 8-oxoG: G or 8-oxoG: T but not 8-oxoG : C pairs. Primer extension reactions in cell-free extracts of M. smegmatis suggested error-prone incorporation of nucleotides into the DNA. Based on these observations, we discuss the physiological role of MutY in specific mutation prevention in mycobacteria.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Society for General Microbiology.
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 09 Mar 2010 07:25
Last Modified: 19 Sep 2010 05:55
URI: http://eprints.iisc.ernet.in/id/eprint/25787

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