Linked Life Data

21762707

Source:http://linkedlifedata.com/resource/pubmed/id/21762707

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-8-25
pubmed:abstractText
To investigate the mechanisms of the therapeutic action and drug resistance to the nitrogen mustard melphalan, melphalan-induced DNA damage repair and chromatin structure were examined along the p53, N-ras and d-globin gene loci in cells carrying different repair activities. In nucleotide excision repair-deficient XP-A cells, similar levels of adducts were found in all fragments examined, indicating uniform distribution of DNA damage. In both, repair-proficient CS-B and XP-C cells, faster repair was observed in regions inside the transcribed N-ras and p53 genes, compared to regions on both sides outside of the genes, while no such difference was observed for the inactive d-globin gene. Moreover, very fast adduct repair on the transcribed strand of the active genes was seen immediately downstream of the transcription start site, together with a steeply decreasing gradient of repair efficiency along the gene towards the 3'-end. In all cells analyzed, the above variation in DNA repair efficiency was paralleled exactly by the variation in the degree of local chromatin condensation, more relaxed chromatin being associated with faster repair. Similar results were obtained using peripheral blood mononuclear cells from healthy volunteers, suggesting that the existence of a repair gradient along transcribed genes may be a universal phenomenon. In conclusion, these findings demonstrate that the repair of melphalan adducts in the transcribed strand of active genes is subject to a strong polarity effect arising from variations in the chromatin structure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0027-5107
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
714
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
78-87
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The repair of melphalan-induced DNA adducts in the transcribed strand of active genes is subject to a strong polarity effect.
pubmed:affiliation
Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't