p53 modulates homologous recombination by transcriptional regulation of the RAD51 gene.
DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild-type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild-type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild-type p53, favoured by DNA damage. Moreover, wild-type p53 inhibits Rad51 foci formation in response to double-strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.
Arias-Lopez
Carmen
C
Centro de Investigaciones Biológicas (CIB-CSIC), Ramiro de Maeztu 9, Madrid 28040, Spain.
Lazaro-Trueba
Iciar
I
Kerr
Peter
P
Lord
Christopher J
CJ
Dexter
Tim
T
Iravani
Marjan
M
Ashworth
Alan
A
Silva
Augusto
A
D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000378:metabolism; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
D005456:Fluorescent Dyes; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D008156:Luciferases; D051135:Rad51 Recombinase