Structure of the Fanconi anaemia monoubiquitin ligase complex.

ABSTRACT: The Fanconi anaemia (FA) pathway repairs DNA damage caused by endogenous and chemotherapy-induced DNA crosslinks, and responds to replication stress^1,2. Genetic inactivation of this pathway by mutation of genes encoding FA complementation group (FANC) proteins impairs development, prevents blood production and promotes cancer^1,3. The key molecular step in the FA pathway is the monoubiquitination of a pseudosymmetric heterodimer of FANCD2-FANCI^4,5 by the FA core complex-a megadalton multiprotein E3 ubiquitin ligase^6,7. Monoubiquitinated FANCD2 then recruits additional protein factors to remove the DNA crosslink or to stabilize the stalled replication fork. A molecular structure of the FA core complex would explain how it acts to maintain genome st

SUBMITTER: Shakeel S 

PROVIDER: S-EPMC6858856 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature