[Mapping of BRCT1 domain of BRCA1 with chromatin unfolding activity].
Breast cancer susceptibility gene 1(BRCA1) plays an important role in breast cancer development and progression. BRCA1 encodes a 1863-amino acid protein with two BRCA1 C-terminal (BRCT) domains at its C-terminus, BRCT1 and BRCT2. Many cancer-predisposing mutations are located in the BRCT domains, which have been shown to induce chromatin unfolding by use of an approach that allows visualization of large-scale chromatin structure through lac repressor/lac operator recognition. To map the important region of BRCT domain (amino acid residues 1642-1736), six deletion mutant constructs were made. The chromatin structure assay showed that amino acid residues 1691-1721 are involved in the induction of chromatin unfolding. To further localize the critical amino acid residues, ten alanine scanning mutant constructs were made. The chromatin structure assay demonstrated that the 1707IAGGK1711 region is critical for the chromatin unfolding activity. Based on the mapped important region, Blast analysis identified a novel homologous protein. Mapping of the BRCT1 domain may aid in the presymptomatic risk assessment and provide a valuable tool for further study on the BRCT1 structure and function.
Ye
Qi-Nong
QN
Beijing Institute of Biotechnology, Beijing 100850, China. yeqn@yahoo.com
Hu
Yan-Fen
YF
Zhong
Hong-Jun
HJ
Li
Rong
R
Huang
Cui-Fen
CF
D019313:BRCA1 Protein / Q000737:chemistry* / Q000502:physiology; D001483:Base Sequence; D002843:Chromatin / Q000737:chemistry*; D003001:Cloning, Molecular; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D013329:Structure-Activity Relationship
D019313:BRCA1 Protein; D002843:Chromatin