Document Detail


Poly(ADP-ribose) synthesis following DNA damage in cells heterozygous or homozygous for the xeroderma pigmentosum genotype.
MedLine Citation:
PMID:  7451457     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Treatment of normal human cells with DNA-damaging agents such as UV light or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stimulates the conversion of NAD to the chromosomal polymer poly(ADP-ribose) which in turn results in a rapid depletion of the cellular NAD pool. We have studied the effect of UV light or MNNG on the NAD pools of seven cell lines of human fibroblasts either homozygous or heterozygous for the xeroderma pigmentosum genotype. Xeroderma pigmentosum cells of genetic complementation groups A, C, and D are deficient in the excision repair of DNA damage caused by UV light. Following UV treatment, the NAD content of these cells was unchanged (complementation groups A and D) or only slightly reduced (complementation group C). Xeroderma pigmentosum cells with the variant genotype have normal excision repair and UV treatment caused a large reduction in the size of the NAD pool. Cell lines derived from asymptomatic, parental heterozygotes of xeroderma pigmentosum complementation groups A and D showed an amount of lowering of NAD following UV treatment that was approximately one-half that of the control cell line. All of the cell lines are able to excise DNA damage caused by MNNG and all of the cell lines had a greatly reduced content of NAD following MNNG treatment. The results demonstrate a close relationship between the conversion of NAD to poly(ADP-ribose) and DNA excision repair in human cells.
Authors:
L S McCurry; M K Jacobson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  256     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1981 Jan 
Date Detail:
Created Date:  1981-03-24     Completed Date:  1981-03-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  551-3     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cell Line
DNA / metabolism*,  radiation effects
DNA Repair
Fibroblasts / drug effects,  metabolism,  radiation effects
Heterozygote*
Homozygote*
Humans
Kinetics
Methylnitronitrosoguanidine / pharmacology
NAD / metabolism
Nucleoside Diphosphate Sugars / biosynthesis*
Poly Adenosine Diphosphate Ribose / biosynthesis*
Ultraviolet Rays
Xeroderma Pigmentosum / genetics*,  metabolism
Grant Support
ID/Acronym/Agency:
CA23994/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Nucleoside Diphosphate Sugars; 26656-46-2/Poly Adenosine Diphosphate Ribose; 53-84-9/NAD; 70-25-7/Methylnitronitrosoguanidine; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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