Linked Life Data

12184783

Source:http://linkedlifedata.com/resource/pubmed/id/12184783

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-8-19
pubmed:abstractText
In response to continuous hydrolytic and oxidative DNA damage, cells of all organisms have a complex network of repair systems that recognize, remove, and rebuild the injured sites. Damaged pyrimidines are generally removed by glycosylases that must scan the entire genome to locate lesions with sufficient fidelity to selectively remove the damage without inadvertent removal of normal bases. We report here studies conducted with a series of base analogues designed to test mechanisms of base recognition suggested by structural studies of glycosylase complexes. The oligonucleotide series examined here includes 5-halouracils with increasing substituent size and purine analogues placed opposite the target uracil with hydrogen, amino, and keto substituents in the 2- and 6-positions. The glycosylases studied here include Escherichia coli uracil-DNA glycosylase (UNG), E. coli mismatch uracil-DNA glycosylase (MUG), and the Methanobacterium thermoautotrophicum mismatch thymine-DNA glycosylase (TDG). The results of this study suggest that these glycosylases utilize several strategies for base identification, including (1) steric limitations on the size of the 5-substituent, (2) electronic-inductive properties of the 5-substituent, (3) reduced thermal stability of mispairs, and (4) specific functional groups on the purine base in the opposing strand. Contrary to predictions based upon the crystal structure, the preference of MUG for mispaired uracil over thymine is not based upon steric exclusion. Furthermore, the preference for mispaired uracil over uracil paired with adenine is more likely due to reduced thermal stability as opposed to specific recognition of the mispaired guanine. On the other hand, TDG, which exhibits modest discrimination among various pyrimidines, shows strong interactions with functional groups present on the purine opposite the target pyrimidine. These results provide new insights into the mechanisms of base selection by DNA repair glycosylases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1001-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Substrate recognition by a family of uracil-DNA glycosylases: UNG, MUG, and TDG.
pubmed:affiliation
Department of Biochemistry and Microbiology, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.