Document Detail

NER and DDR: classical music with new instruments.
MedLine Citation:
PMID:  22373527     Owner:  NLM     Status:  MEDLINE    
Genomic insults by endogenous or exogenous sources activate the DNA damage response (DDR). After the recognition of damaged DNA by specific factors, repair mechanisms process the lesions, and a surveillance mechanism, known as DNA damage checkpoint, is triggered by single-stranded (ss) DNA covered by RPA. UV light induces DNA lesions, mainly 6,4 photoproducts (6-4PP) and cyclobutane pyrimidine dimers (CPD), which are removed by nucleotide excision repair (NER). Recent reports shed light onto the mechanism connecting NER and DDR after UV irradiation. How does UV-induced DNA damage activate checkpoint kinases? How is ssDNA generated at UV lesions? In yeast, UV lesions persisting during S phase represent a block for the advancing of replication forks, which temporarily stop and then reinitiate downstream of the damage, leaving a ssDNA region containing the lesion. Nonreplicating yeast and human cells with defects in NER are not able to properly activate the checkpoint cascade, indicating that processing of UV lesions is a prerequisite for checkpoint activation. This pathway also requires the function of exonuclease 1, which acts on NER intermediates generating long tracts of ssDNA. Here, we review the connections between NER processing of UV-induced lesions and checkpoint activation, discussing the role of recently identified players in this mechanism.
Sarah Sertic; Sara Pizzi; Federico Lazzaro; Paolo Plevani; Marco Muzi-Falconi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-29     Completed Date:  2012-09-14     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  668-74     Citation Subset:  IM    
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MeSH Terms
Cell Cycle Checkpoints / drug effects,  genetics
DNA Breaks, Single-Stranded / radiation effects
DNA Damage / genetics*,  radiation effects
DNA Repair / genetics,  physiology*
Exodeoxyribonucleases / genetics,  metabolism
Ultraviolet Rays / adverse effects
Grant Support
Reg. No./Substance:
EC 3.1.-/Exodeoxyribonucleases; EC I

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