ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair |
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Authors: | Bleuyard Jean-Yves Buisson Rémi Masson Jean-Yves Esashi Fumiko |
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Institution: | Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK. |
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Abstract: | 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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Keywords: | PALB2 chromatin association homologous recombination DNA repair cancer |
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