BLM helicase-dependent and -independent roles of 53BP1 during replication stress-mediated homologous recombination.
Mutations in BLM helicase cause Bloom syndrome, characterized by predisposition to all forms of cancer. We demonstrate that BLM, signal transducer 53BP1, and RAD51 interact during stalled replication. Interactions between the three proteins have functional consequences. Lack of 53BP1 decreases the cell survival and enhanced chromosomal aberration after replication arrest. 53BP1 exhibits both BLM-dependent and -independent anti-recombinogenic functions in human and mouse cells. Both BLM and 53BP1 abrogate endogenous RAD51 foci formation and disrupt RAD51 polymerization. Consequently, loss of BLM and 53BP1 synergistically enhances stress-dependent homologous recombination. These results provide evidence regarding the cooperation between BLM and 53BP1 during maintenance of genomic integrity.
Tripathi
Vivek
V
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Nagarjuna
Tirunelvely
T
Sengupta
Sagar
S
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D053484:RecQ Helicases; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange / Q000235:genetics; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1
D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D006918:Hydroxyurea