The goal of the lab’s current work is to understand the function of FA / BRCA proteins in DNA damage responses and to apply this knowledge to improving approaches to cancer therapy.
At present, 15 FA genes have been identified. Eight of the FA genes form a nuclear core complex that is required for the monoubiquitination of FANCD2, which is a key step in the FA-BRCA pathway, and of FANCI. We are particularly interested in the function and regulation of FANCD2 in DNA damage responses.
Some of the BRCA genes, including FANCJ / BRIP1, FANCN / PALB2, FANCD1 / BRCA2 and FANCO / RAD51C, are also FA genes but are not required for FANCD2 monoubiquitination. We seek to elucidate their functional relationships to other FA proteins, something that is not well understood at present. BRIP1 is a helicase first identified by its association with another breast cancer susceptibility protein, BRCA1. PALB2 regulates the recruitment of BRCA2 to sites of DNA damage, and both have a critical role in regulating DNA repair by homologous recombination. RAD51C is a paralog of the RAD51 protein that has an integral role in homologous recombination and which is regulated by BRCA2.
FANCD2 monoubiquitination in DNA damage responses
NIH R01 HL085587 (PI: Paul Andreassen)
National Heart, Lung and Blood Institute
Through June 30, 2014