Pir51, a Rad51-interacting protein with high expression in aggressive lymphoma, controls mitomycin C sensitivity and prevents chromosomal breaks.
Pir51, a protein of unknown function that interacts with Rad51, was identified in a screen for genes that were highly expressed in aggressive mantle cell lymphoma (MCL) versus indolent small lymphocytic lymphoma (SLL) patient samples. We show that Pir51 is a nuclear protein expressed in a variety of cell types and that its expression is regulated during the cell cycle in a pattern nearly identical to Rad51. Also similar to Rad51, Pir51 levels did not change in response to a variety of DNA damaging agents. siRNA depletion of Pir51 did not reduce homologous recombination repair (HRR), but sensitized cells to mitomycin C (MMC)-induced DNA crosslinking and resulted in elevated levels of double-strand breaks (DSBs) in metaphase chromosome spreads and reduced colony formation. Therefore, Pir51 maintains genomic integrity and potentially connects the early response to DNA crosslinks, orchestrated by the ATR kinase and Fanconi Anemia (FA) proteins, to later stages of Rad51-dependent repair. Our results provide the first example of a Rad51-binding protein that influences DNA crosslink repair without affecting homologous recombination repair.
Henson
Sarah E
SE
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Tsai
Shih-Chang
SC
Malone
Cindy Sue
CS
Soghomonian
Shahe V
SV
Ouyang
Yan
Y
Wall
Randolph
R
Marahrens
York
Y
Teitell
Michael A
MA
D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019457:Chromosome Breakage / Q000187:drug effects*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism; D016685:Mitomycin / Q000378:metabolism / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D051135:Rad51 Recombinase / Q000378:metabolism
D004268:DNA-Binding Proteins; C110410:RAD51AP1 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016685:Mitomycin; D051135:Rad51 Recombinase