Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.
Homologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.
Dray
Eloïse
E
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, USA. eloise.dray@yale.edu
Etchin
Julia
J
Wiese
Claudia
C
Saro
Dorina
D
Williams
Gareth J
GJ
Hammel
Michal
M
Yu
Xiong
X
Galkin
Vitold E
VE
Liu
Dongqing
D
Tsai
Miaw-Sheue
MS
Sy
Shirley M-H
SM
Schild
David
D
Egelman
Edward
E
Chen
Junjie
J
Sung
Patrick
P
D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000737:chemistry / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology*; D004273:DNA, Neoplasm / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D006801:Humans; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000502:physiology; D011995:Recombination, Genetic / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000076164:Fanconi Anemia Complementation Group N Protein; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D010446:Peptide Fragments; C110410:RAD51AP1 protein, human; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; C495153:RAD51 protein, human; D051135:Rad51 Recombinase