ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair.

نویسندگان

  • Jean-Yves Bleuyard
  • Rémi Buisson
  • Jean-Yves Masson
  • Fumiko Esashi
چکیده

The partner and localizer of breast cancer 2 susceptibility protein (PALB2) is crucial for the repair of DNA damage by homologous recombination. Here, we report that chromatin-association motif (ChAM), an evolutionarily conserved motif in PALB2, is necessary and sufficient to mediate its chromatin association in both unperturbed and damaged cells. ChAM is distinct from the previously described PALB2 DNA-binding regions. Deletion of ChAM decreases PALB2 and Rad51 accumulation at DNA damage sites and confers cellular hypersensitivity to the genotoxic drug mitomycin C. These results suggest that PALB2 chromatin association via ChAM facilitates PALB2 function in the cellular resistance to DNA damage.

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Perturbation of PALB2 function by the T413S mutation

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Germline mutations in the gene are associated with the genetic Background: PALB2 disorder Fanconi anaemia and increased predisposition to cancer. Disease-associated variants are mainly protein-truncating mutations, whereas a few missense substitutions are reported to perturb its interaction with breast cancer susceptibility proteins BRCA1 and BRCA2, which play essential roles in homology-direct...

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عنوان ژورنال:
  • EMBO reports

دوره 13 2  شماره 

صفحات  -

تاریخ انتشار 2012