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Substrate specificities and functional characterization of a thermo-tolerant uracil DNA glycosylase (UdgB) from Mycobacterium tuberculosis

Srinath, Thiruneelakantan and Bharti, Sanjay Kumar and Varshney, Umesh (2007) Substrate specificities and functional characterization of a thermo-tolerant uracil DNA glycosylase (UdgB) from Mycobacterium tuberculosis. In: DNA Repair, 6 (10). pp. 1517-1528.

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Abstract

Uracil DNA glycosylases (UDGs) excise uracil from DNA and initiate the base (uracil) excision repair pathway. Ung, a highly conserved protein, is the only UDG characterized so far in mycobacteria. Here, we show that Rv1259 from Mycobacterium tuberculosis codes for a double-stranded DNA (dsDNA) specific UDG (MtuUdgB). MtuUdgB is thermo-tolerant, contains Fe–S cluster and, in addition to uracil, it excises ethenocytosine and hypoxanthine from dsDNA. MtuUdgB is product inhibited by AP-site containing dsDNA but not by uracil. While MtuUdgB excises uracil present as a single-nucleotide bulge in dsDNA, it is insensitive to inhibition by dsDNA containing AP-site in the bulge. Interestingly, in the presence of cellular factors, the uracil excision activity of MtuUdgB is enhanced, and when introduced into E. coli (ung−), it rescues its mutator phenotype and prevents C to T mutations in DNA. Novel features of the mechanism of action of MtuUdgB and the physiological significance of the family 5 UDG in mycobacteria have been discussed.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier B.V.
Keywords: Family 5 UDG;Fe–S cluster;Ethenocytosine;Hypoxanthine
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 15 Nov 2007
Last Modified: 19 Sep 2010 04:41
URI: http://eprints.iisc.ernet.in/id/eprint/12504

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