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.
Linke
Steven P
SP
Laboratories of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Sengupta
Sagar
S
Khabie
Nissim
N
Jeffries
Beth A
BA
Buchhop
Sabine
S
Miska
Stefan
S
Henning
Wilhelm
W
Pedeux
Remy
R
Wang
Xin W
XW
Hofseth
Lorne J
LJ
Yang
Qin
Q
Garfield
Susan H
SH
Stürzbecher
Horst-Werner
HW
Harris
Curtis C
CC
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