Fanconi anemia and ubiquitination.
Fanconi anemia (FA) is a rare recessive hereditary disease characterized clinically by congenital defects, progressive bone-marrow failure, and cancer predisposition. Cells from FA patients exhibit hypersensitivity to DNA cross-linking agents, such as mitomycin C (MMC). To date, at least 12 FA genes have been found deleted or mutated in FA cells, and 10 FA gene products form a core complex involved in FA/BRCA2 DNA repair pathway?FA pathway. The ubiquitin E3 ligase FANCL, an important factor of FA core complex, co-functions with a new ubiquitin conjugating enzyme UBE2T to catalyze the monoubiquitination of FANCD2. FANCD2-Ub binds BRCA2 to form a new complex located in chromatin foci and then take part in DNA repair process. The deubiquitylating enzyme USP1 removes the mono-ubiquitin from FANCD2-Ub following completion of the repair process, then restores the blocked cell cycle to normal order by shutting off the FA pathway. In a word, the FANCD2 activity adjusted exquisitely by ubiquitination and/or deubiquitination in vivo may co-regulate the FA pathway involving in variant DNA repair pathway.
Zhang
Yingying
Y
Beijing Institute of Biotechnology, Beijing 100071, China.
Zhou
Xiaowei
X
Huang
Peitang
P
D005199:Fanconi Anemia / Q000378:metabolism*; D052240:Fanconi Anemia Complementation Group L Protein / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination
D044763:Ubiquitin-Conjugating Enzymes; D052240:Fanconi Anemia Complementation Group L Protein