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.
|Original language||English (US)|
|Number of pages||12|
|Journal||Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis|
|State||Published - Oct 10 2006|
Bibliographical noteFunding Information:
We thank Maria Jasin (Memorial Sloan Kettering Cancer Center) for providing p59xDR-GFP6 and pCBASce constructs for HRR assays, the UCLA flow cytometry facility, Francesca M. Fike for excellent technical assistance, Robert Schiestl and Jennifer Salstrom for comments on the manuscript, and members of the Wall, Marahrens and Teitell labs for many helpful discussions. This work was supported by NIH grants GM40185 (R.W.), CA85841 (R.W.), HD41451 (Y.M.), CA90571 (M.A.T) and CA107300 (M.A.T). S.E.H. was supported by USPHS Award GM07185. The Teitell lab is also supported by CMISE, a NASA URETI Institute (NCC 201364) and M.A.T. is a Scholar of the Leukemia and Lymphoma Society.
- Cell cycle
- DNA repair