Document Detail


Repair in haploid male germ cells occurs late in differentiation as chromatin is condensing.
MedLine Citation:
PMID:  12684825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Huntington's Disease (HD) is one of eight progressive neurodegenerative disorders in which the underlying mutation is a CAG expansion encoding a polyglutamine tract. The mechanism of trinucleotide expansion remains poorly understood. We have followed heritable changes in CAG length in male transgenic mice. In germ cells, expansion is limited to the post-meiotic, haploid cell and therefore cannot involve mitotic replication or recombination between a homologous chromosome and a sister chromatid. Expansion occurs by gap filling synthesis when DNA loops comprising the CAG trinucleotide repeats are sealed into the DNA strand. Our data support a model in which expansion occurs late in male germ cell development as spermatids are entering the epididymis at a time when chromatin is condensing. These data indicate that repair can be carried out in germ cells as long as the DNA is accessible. The capacity for repair of germ cells may have important implications for future gene therapy.
Authors:
C T McMurray; I V Kortun
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Publication Detail:
Type:  Journal Article; Review     Date:  2003-04-04
Journal Detail:
Title:  Chromosoma     Volume:  111     ISSN:  0009-5915     ISO Abbreviation:  Chromosoma     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-13     Completed Date:  2004-02-11     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  2985138R     Medline TA:  Chromosoma     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  505-8     Citation Subset:  IM    
Affiliation:
Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. mcmurray.cynthia@mayo.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatin / genetics*,  physiology
DNA / physiology
DNA Damage
DNA Repair / genetics*,  physiology
Humans
Male
Mice
Mice, Transgenic
Spermatogenesis / physiology*
Spermatozoa / physiology*
Chemical
Reg. No./Substance:
0/Chromatin; 9007-49-2/DNA

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


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