BRCT domain, from T.Thermophilus DNA Ligase

BRCA-1 is on the long arm of chromosome 17, and has been identified as a gene which predisposes women to these types of cancer.The BRCT domain is the C-terminal portion of the BRCA-1 gene. Many mutant alleles have been mapped to this region of the protein. BRCT seems to be conserved across multiple organisms, usually in cell cycle regulation and DNA repair genes. In many mammalian genes that contain BRCT, these domains appear as - multiple tandem repeats at the end of the gene, as show in the figure to the left.

Most of the proteins in this BRCT family are involved in cell-cycle regulation or DNA repair, suggesting a role for the BRCT domain in these pathways. The BRCT domain seems to function as a protein-protein interacting moiety. A heterodimeric complex, involving proteins that interacts through their respective BRCT domains, has been identified, XRCC1/DNA ligase III [14, 15]. The significance of these interactions will provide clues to the molecular basis that underlies cell-cycle regulation and DNA repair.

Although they share little sequence identity, the solved BRCT structures from XRCC1, BRCA-1, and H. sapiens DNA ligase III share a similar fold of a central b-sheet with multiple surrounding a-helices. The H. sapiens DNA ligase III has only 2 surrounding a-helices, whereas the other structures have 3 surrounding a-helices. As later discovered, the BRCT structure of T. thermophilus DNA ligase also shares the same fold of a central b-sheet with 3 surrounding a-helices.


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