Document Detail

Homologous recombination conserves DNA sequence integrity throughout the cell cycle in embryonic stem cells.
MedLine Citation:
PMID:  20491544     Owner:  NLM     Status:  MEDLINE    
The maintenance of genomic integrity is crucial to embryonic stem cells (ESC) considering the potential for propagating undesirable mutations to the resulting somatic and germ cell lineages. Indeed, mouse ESC (mESC) exhibit a significantly lower mutation frequency compared to differentiated cells. This could be due to more effective elimination of genetically damaged cells via apoptosis, or especially robust, sequence-conserving DNA damage repair mechanisms such as homologous recombination (HR). We used fluorescence microscopy and 3-dimensional image analysis to compare mESC and differentiated cells, with regard to HR-mediated repair of spontaneous and X-ray-induced double-strand breaks (DSBs). Microscopic analysis of repair foci, flow cytometry, and functional assays of the major DSB repair pathways indicate that HR is greater in mESC compared to fibroblasts. Strikingly, HR appears to be the predominant pathway choice to repair induced or spontaneous DNA damage throughout the ESC cycle in contrast to fibroblasts, where it is restricted to replicated chromatin. This suggests that alternative templates, such as homologous chromosomes, are more frequently used to repair DSB in ESC. Relatively frequent HR utilizing homolog chromosome sequences preserves genome integrity in ESC and has distinctive and important genetic consequences to subsequent somatic and germ cell lineages.
Lourdes Serrano; Li Liang; Yiming Chang; Li Deng; Christopher Maulion; Son Nguyen; Jay A Tischfield
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-10-29
Journal Detail:
Title:  Stem cells and development     Volume:  20     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-24     Completed Date:  2011-06-24     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-74     Citation Subset:  IM    
Department of Genetics, Human Genetics Institute, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854-8082, USA.
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MeSH Terms
Cell Cycle / genetics*
Cells, Cultured
DNA / metabolism*
DNA Breaks, Double-Stranded
DNA Damage
DNA Repair*
Deoxyuridine / analogs & derivatives,  metabolism
Embryonic Stem Cells / metabolism*
Fibroblasts / metabolism
Histones / metabolism
Rad51 Recombinase / metabolism
Recombination, Genetic*
Grant Support
Reg. No./Substance:
0/Histones; 0/gamma-H2AX protein, mouse; 61135-33-9/5-ethynyl-2'-deoxyuridine; 9007-49-2/DNA; 951-78-0/Deoxyuridine; EC 2.7.7.-/Rad51 Recombinase; EC 2.7.7.-/Rad51 protein, mouse

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