The anaphase promoting complex impacts repair choice by protecting ubiquitin signalling at DNA damage sites.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28604711.
- Also identified by DOI 10.1038/ncomms15751 and PMC identifier 5472795.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Double-strand breaks (DSBs) are repaired through two major pathways, homology-directed recombination (HDR) and non-homologous end joining (NHEJ). While HDR can only occur in S/G2, NHEJ can happen in all cell cycle phases (except mitosis). How then is the repair choice made in S/G2 cells? Here we provide evidence demonstrating that APC<sup>Cdh1</sup> plays a critical role in choosing the repair pathways in S/G2 cells. Our results suggest that the default for all DSBs is to recruit 53BP1 and RIF1. BRCA1 is blocked from being recruited to broken ends because its recruitment signal, K63-linked poly-ubiquitin chains on histones, is actively destroyed by the deubiquitinating enzyme USP1. We show that the removal of USP1 depends on APC<sup>Cdh1</sup> and requires Chk1 activation known to be catalysed by ssDNA-RPA-ATR signalling at the ends designated for HDR, linking the status of end processing to RIF1 or BRCA1 recruitment.
Medical subject headings
- Anaphase-Promoting Complex-Cyclosome
- DNA Damage
- DNA Repair
- Ubiquitin