RGD Reference Report - Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks. - Rat Genome Database

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Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks.

Authors: Stante, M  Minopoli, G  Passaro, F  Raia, M  Vecchio, LD  Russo, T 
Citation: Stante M, etal., Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5093-8. doi: 10.1073/pnas.0810869106. Epub 2009 Mar 12.
RGD ID: 8553580
Pubmed: PMID:19282473   (View Abstract at PubMed)
PMCID: PMC2664056   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0810869106   (Journal Full-text)

Fe65 is a binding partner of the Alzheimer's beta-amyloid precursor protein APP. The possible involvement of this protein in the cellular response to DNA damage was suggested by the observation that Fe65 null mice are more sensitive to genotoxic stress than WT counterpart. Fe65 associated with chromatin under basal conditions and its involvement in DNA damage repair requires this association. A known partner of Fe65 is the histone acetyltransferase Tip60. Considering the crucial role of Tip60 in DNA repair, we explored the hypothesis that the phenotype of Fe65 null cells depended on its interaction with Tip60. We demonstrated that Fe65 knockdown impaired recruitment of Tip60-TRRAP complex to DNA double strand breaks and decreased histone H4 acetylation. Accordingly, the efficiency of DNA repair was decreased upon Fe65 suppression. To explore whether APP has a role in this mechanism, we analyzed a Fe65 mutant unable to bind to APP. This mutant failed to rescue the phenotypes of Fe65 null cells; furthermore, APP/APLP2 suppression results in the impairment of recruitment of Tip60-TRRAP complex to DNA double strand breaks, decreased histone H4 acetylation and repair efficiency. On these bases, we propose that Fe65 and its interaction with APP play an important role in the response to DNA damage by assisting the recruitment of Tip60-TRRAP to DNA damage sites.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Apbb1RatDNA repair-dependent chromatin remodeling involved_inIMP PMID:19282473UniProt 
Kat5RatDNA repair-dependent chromatin remodeling involved_inNAS PMID:19282473UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Apbb1Ratnucleus located_inIDA PMID:19282473UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Kat5Rathistone acetyltransferase activity enablesNAS PMID:19282473UniProt 
Apbb1Ratprotein binding enablesIPIUniProtKB:Q99MK2PMID:19282473UniProt 
Kat5Ratprotein binding enablesIPIUniProtKB:P46933PMID:19282473UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Apbb1  (amyloid beta precursor protein binding family B member 1)
Kat5  (lysine acetyltransferase 5)


Additional Information