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Tumor suppressor protein PALB2 has strand exchange activity independent of recombinase Rad51
Author(s) -
Deveryshetty Jaigeeth,
Kanikkannan Lakshmi,
Korolev Sergey,
Doisy E. A.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb6
Subject(s) - palb2 , rad51 , recombinase , homologous recombination , dna damage , dna repair , dna , biology , genetics , microbiology and biotechnology , cancer research , chemistry , mutation , gene , recombination , germline mutation
PALB2 ( P artner a nd L ocalizer of B RCA 2 ) is recombination mediator protein (RMP) involved in homology dependent repair (HDR) of double strand breaks (DSB). PALB2 works synergistically with BRCA2 by promoting Rad51 recombinase filament formation on single‐stranded (ss) DNA to initiate strand exchange essential for HDR. Numerous inherited PLAB2 mutations are reported to predispose to cancers such as breast and pancreatic cancers and rare genetic disease, Fanconi Anemia. However, the molecular mechanism PALB2 function is not well characterized. Here we report the DNA binding properties of PALB2 DNA‐binding domain (DBD), affinity and stoichiometry of interaction with various DNA substrates and identify residues involved in DNA binding. Further, we report an unanticipated activity of PALB2, where PALB2 promoted strand exchange in the absence of recombinase. This activity was enhanced in the presence of recombinase Rad51 and is abolished upon mutations of PALB2 DNA‐binding residues. Several properties also resemble those reported for Rad52. Our study demonstrates that PALB2 has multiple roles in homologous DNA repair. Support or Funding Information Siteman Cancer center This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .