Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.

ABSTRACT: Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (I_Ub D2). Here, we present a 4.1 Å cryo-EM structure of I_Ub D2 complex bound to double-stranded DNA. We show that this complex, like ID2_Ub and I_Ub D2_Ub , is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the I_Ub D2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ub

SUBMITTER: Lemonidis K 

PROVIDER: S-EPMC9890228 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature