Regulation of the Fanconi Anemia Pathway by Deubiquitination
Contributors: D'Andrea, Alan D.; Finley, Daniel J.; Walter, Johannes; Harper, J. Wade; Gill, Grace
Published: 2012
Language: eng
Description: Fanconi anemia (FA) is a rare genetic disease characterized by bone marrow failure and cancer predisposition. Cell lines derived from FA patient exhibit chromosomal instability and sensitivity to DNA interstand crosslinkers (ICLs) like mitomycin (MMC). The key event in Fanconi anemia pathway is the regulated ubiquitination and deubiquitination of FANCD2 and FANCI. Upon DNA damage, FANCD2 and FANCI are monoubiquitinated by FA core complex. They then move into the chromatin and serve as the landing site for downstream players, like FANCP/SLX4 and FAN1. USP1, the deubiquitinating enzyme (DUB), removes ubiquitin from FANCD-Ub/FANCI-Ub, and this step is required for the integrity of FA pathway.
Notes: Keywords: Deubiquitination, DNA Repair, Fanconi Anemia, SUMO, Ubiquitination, Ubiquitin-binding Domain.

Thesis Ph.D. Harvard University 2012