Linked Life Data

21241706

Source:http://linkedlifedata.com/resource/pubmed/id/21241706

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-2-21
pubmed:abstractText
Chronic inflammation is known to lead to an increased risk for the development of cancer. Under inflammatory condition, cellular DNA is damaged by hypobromous acid, which is generated by myeloperoxidase and eosinophil peroxidase. The reactive brominating species induced brominated DNA adducts such as 8-bromo-2'-deoxyguanosine (8-Br-dG), 8-bromo-2'-deoxyadenosine (8-Br-dA), and 5-bromo-2'-deoxycytidine (5-Br-dC). These DNA lesions may be implicated in carcinogenesis. In this study, we analyzed the miscoding properties of the brominated DNA adducts generated by human DNA polymerases (pols). Site-specifically modified oligodeoxynucleotides containing a single 8-Br-dG, 8-Br-dA, or 5-Br-dC were used as a template in primer extension reactions catalyzed by human pols ?, ?, and ?. When 8-Br-dG-modified template was used, pol ? primarily incorporated dCMP, the correct base, opposite the lesion, along with a small amount of one-base deletion (4.8%). Pol ? also promoted one-base deletion (14.2%), accompanied by misincorporation of dGMP (9.5%), dAMP (8.0%), and dTMP (6.1%) opposite the lesion. Pol ?, on the other hand, readily bypassed the 8-Br-dG lesion in an error-free manner. As for 8-Br-dA and 5-Br-dC, all the pols bypassed the lesions and no miscoding events were observed. These results indicate that only 8-Br-dG, and not 5-Br-dC and 8-Br-dA, is a mutagenic lesion; the miscoding frequency and specificity vary depending on the DNA pol used. Thus, hypobromous acid-induced 8-Br-dG adduct may increase mutagenic potential at the site of inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
406
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-86
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Mutational specificities of brominated DNA adducts catalyzed by human DNA polymerases.
pubmed:affiliation
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't