Document Detail


Activation of fanconi anemia pathway in cells with re-replicated DNA.
MedLine Citation:
PMID:  17102625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To maintain genome stability, the cell has to limit initiation of DNA replication to once per cell cycle. Loss of this control leads to DNA rereplication with repeated firing of replication origins in the same cell cycle. Rereplication generates both ssDNA and double strand breaks, as well as activation of the DNA damage checkpoint. In rereplicated cells, activation of the checkpoint is critical to arrest cells in G(2) resulting in accumulation of cells with rereplicated DNA. Abrogation of this checkpoint suppresses the progressive accumulation of cells with excess DNA and causes apoptosis. Recently, the Fanconi Anemia pathway was reported to be activated in rereplicating cells. Interestingly, FA core complexes but not FANCD2, is required for checkpoint activation in rereplicated cells, suggesting that the pathway to checkpoint activation requires the ubiquitination of substrates other than FANCD2. In addition, FANCD2 is required for recruitment of Rad51 to foci in rereplicated cells, so that the repair pathways activated after small degrees of rereplication are expected to be compromised in cells with mutations in the FA pathway.
Authors:
Wenge Zhu; Anindya Dutta
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-10-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  5     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-03     Revised Date:  2011-05-06    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2306-9     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
DNA Damage*
DNA Repair
DNA Replication*
Fanconi Anemia / genetics,  metabolism*,  pathology
Fanconi Anemia Complementation Group D2 Protein / physiology
Humans
Interphase
Mutation
Signal Transduction
Grant Support
ID/Acronym/Agency:
CA60499/CA/NCI NIH HHS; R01 CA060499-13/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Fanconi Anemia Complementation Group D2 Protein

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


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