title: ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair.
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.
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Bleuyard
authors.forename: Rémi
authors.initials: R
authors.lastname: Buisson
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Masson
authors.forename: Fumiko
authors.initials: F
authors.lastname: Esashi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D019143:Evolution, Molecular; D000076164:Fanconi Anemia Complementation Group N Protein; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; D009707:Nucleosomes; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins