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.