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 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 (IUbD2). Here, we present a 4.1 Å cryo-EM structure of IUbD2 complex bound to double-stranded DNA. We show that this complex, like ID2Ub and IUbD2Ub, is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the IUbD2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ubiquitination in the ID2Ub-DNA complex. The IUbD2-DNA complex exhibits deub

SUBMITTER: Dr. Kimon Lemonidis 

PROVIDER: S-SCDT-10_15252-EMBJ_2022111898 | biostudies-other |

REPOSITORIES: biostudies-other