p53 interacts with hRAD51 and hRAD54, and directly modulates homologous recombination.
p53 inhibits tumorigenesis through a variety of functions, including mediation of cell cycle arrest, premature senescence, and apoptosis.p53 also can associate with several DNA helicases and proteins involved in homologous recombination. In this study, we show that p53, hRAD51, and hRAD54 coimmunoprecipitated and colocalized with each other at endogenous levels in normal cells. Colocalization was observed with the phosphoserine-15 form of p53 at presumed DNA processing sites after the induction of DNA breaks. hRAD54 bound directly to the p53 COOH terminus in vitro without a nucleic acid intermediate. We then investigated the functional consequences of these protein interactions. A host cell reactivation assay revealed that the elevation in recombination observed after p53 inactivation is dependent on the hRAD51 pathway and that p53-dependent antirecombinogenic activity can be attributed to p53 binding to hRAD51 directly. These data support the hypothesis that p53 helps maintain genetic stability through transcription-independent modulation of homologous recombination factors.
Laboratories of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Steven P
SP
Linke
Sagar
S
Sengupta
Nissim
N
Khabie
Beth A
BA
Jeffries
Sabine
S
Buchhop
Stefan
S
Miska
Wilhelm
W
Henning
Remy
R
Pedeux
Xin W
XW
Wang
Lorne J
LJ
Hofseth
Qin
Q
Yang
Susan H
SH
Garfield
Horst-Werner
HW
Stürzbecher
Curtis C
CC
Harris
D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D004265:DNA Helicases; C103532:RAD54L protein, human