Substrate specificities and functional characterization of a thermo-tolerant uracil DNA glycosylase (UdgB) from Mycobacterium tuberculosis.
DNA Repair (Amst)
; 6(10): 1517-28, 2007 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-17588829
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Uracil-DNA Glycosidase
/
Mycobacterium tuberculosis
Language:
En
Journal:
DNA Repair (Amst)
Journal subject:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Year:
2007
Document type:
Article
Affiliation country: