ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair.
نویسندگان
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.
منابع مشابه
Perturbation of PALB2 function by the T413S mutation
Germline mutations in the gene are associated with the Background: PALB2 genetic 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-dire...
متن کاملPerturbation of PALB2 function by the T413S mutation found in small cell lung cancer [version 1; referees: awaiting peer review]
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...
متن کاملPerturbation of PALB 2 function by the T 413 S mutation found in small cell lung cancer
Germline mutations in the gene are associated with the Background: PALB2 genetic 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-dire...
متن کاملPerturbation of PALB2 function by the T413S mutation found in small cell lung cancer
Background: Germline mutations in the PALB2 gene are associated with the genetic 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...
متن کاملMRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks.
PALB2 physically and functionally connects the proteins encoded by the BRCA1 and BRCA2 breast and ovarian cancer genes into a DNA-damage-response network. However, it remains unclear how these proteins associate with chromatin that contains damaged DNA. We show here that PALB2 binds directly to a conserved chromodomain protein, MRG15, which is a component of histone acetyltransferase-deacetylas...
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ورودعنوان ژورنال:
- EMBO reports
دوره 13 2 شماره
صفحات -
تاریخ انتشار 2012