Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2023 Oct 3;43(10):BSR20222591. doi: 10.1042/BSR20222591

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© 2023 The Author(s).

This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

PMC Copyright notice

(A) The removal of DNA–protein cross-links (DPCs) relies mainly on TRAIP/proteasomes (top), which degrade polyubiquitinated DPCs, or SPRTN (bottom), which is recruited by ubiquitinated PCNA and deubiquinated by USP7. (B) Interstrand cross-link (ICL) removal is mainly mediated by the FA pathway. When two replication forks converge on an ICL, TRAIP-generated Ub chains recruit the glycosylase NEIL3 to directly cleave cross-links, while longer Ub chains promote CDC48/p97-dependent CMG disassembly. Next, a heterotetrameric FANCM complex recognizes the stressed replication forks and recruits the FA core complex. Within the core complex, FANCL (E3 ubiquitin ligase) and FANCT (E2) monoubiquitinate FANCD2 at K561 and FANCI at K523. This step promotes the nuclease-dependent DNA incision by XPF (FANCQ)-ERCC1 and SLX4 (FANCP), leading to the unhooking of ICLs and generation of DSB intermediates.