Document Detail

Role and regulation of human XRCC4-like factor/cernunnos.
MedLine Citation:
PMID:  18335491     Owner:  NLM     Status:  MEDLINE    
In mammalian cells, non-homologous end joining (NHEJ) is the major double strand break (DSB) repair mechanism during the G(1) phase of the cell cycle. It also contributes to DSB repair during the S and G(2) phases. Ku heterodimer, DNA PKcs, XRCC4 and DNA Ligase IV constitute the core NHEJ machinery, which joins directly ligatable ends. XRCC4-like factor/Cernunnos (XLF/Cer) is a recently discovered interaction partner of XRCC4. Current evidence suggests the following model for the role of XLF/Cer in NHEJ: after DSB induction, the XRCC4-DNA Ligase IV complex promotes efficient accumulation of XLF/Cer at DNA damage sites via constitutive interaction of the XRCC4 and XLF/Cer head domains and dependent on components of the DNA PK complex. Ku alone can stabilise the association of XLF/Cer with DNA ends. XLF/Cer stimulates ligation of complementary and non-complementary DNA ends by XRCC4-DNA Ligase IV. This activity involves the carboxy-terminal DNA binding region of XLF/Cer and could occur via different, non-exclusive modes: (i) enhancement of the stability of the XRCC4-DNA Ligase IV complex on DNA ends by XLF/Cer, (ii) modulation of the efficiency and/or specificity of DNA Ligase IV by binding of XLF/Cer to the XRCC4-DNA Ligase IV complex, (iii) promotion of the alignment of blunt or other non-complementary DNA ends by XLF/Cer for ligation. XLF/Cer promotes the preservation of 3' overhangs, restricts nucleotide loss and thereby promotes accuracy of DSB joining by XRCC4-DNA Ligase IV during NHEJ and V(D)J recombination.
Kirsten Dahm
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  104     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-10-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1534-40     Citation Subset:  IM    
Genome Damage and Stability Centre, University of Sussex, BN19RQ Brighton, UK.
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MeSH Terms
DNA / metabolism
DNA Repair Enzymes / metabolism*
DNA-Binding Proteins / metabolism*
Protein Binding
Recombination, Genetic
Reg. No./Substance:
0/DNA-Binding Proteins; 0/NHEJ1 protein, human; 9007-49-2/DNA; EC 6.5.1.-/DNA Repair Enzymes

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

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