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BRCA 1, a breast cancer susceptibility gene, encodes a nuclear phosphoprotein of 1863 amino acid residues.The BRCA1 protein participates in genomic integrity maintenance through multiple functions in DNA damage repair, cell cycle checkpoint, protein ubiquitination and transcriptional regulation.It is characterized into 3 major domains, including the N-terminal zinc finger RING domain (BRCA1 RING domain), the large central segment, and the BRCA1 Cterminal domain (BRCT).In this study, we demonstrated the in vitro platination of the BRCA1 RING protein and the 3-terminal region of the human BRCA1 by the anticancer platinum drug cisplatin.BRCA1 protein contained a preformed structure in the apo-form with structural changes and more resistance to limited proteolysis after Zn2+ bind ing.SDS-PAGE and mass spectrometric analyses revealed that the drug formed monofunctional and bifunctional BRCA 1 adducts.Preferential binding of platinum (Ⅱ) to His 117 of the BRCA1 peptide [1] Glu-Asn-Asn-Ser-Pro-GluHis-Leu-Lys119 was observed.CD spectra showed that the apo-form, not holo-form, of BRCA1 underwent more folded structural rearrangement with the retention of protein structure upon cisplatin binding.Cisplatin-bound protein exhibited an enhanced thermostability by 13℃, resulting from the favourably intermolecular crosslinks driven by the free energy.