Fanconi anemia and ubiquitination.

Abstract

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.

• Authors: Yingying Zhang, Xiaowei Zhou, Peitang Huang
• Journal: Journal of genetics and genomics = Yi chuan xue bao (J Genet Genomics) Vol. 34 Issue 7 Pg. 573-80 (Jul 2007) ISSN: 1673-8527 [Print] China
• PMID: 17643942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Ubiquitin-Conjugating Enzymes
• Fanconi Anemia Complementation Group L Protein

Topics

• Fanconi Anemia (metabolism)
• Fanconi Anemia Complementation Group L Protein (metabolism)
• Humans
• Signal Transduction
• Ubiquitin-Conjugating Enzymes (metabolism)
• Ubiquitination