PCNA promotes processive DNA end resection by Exo1
Open Access
- 10 August 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (20), 9325-9338
- https://doi.org/10.1093/nar/gkt672
Abstract
Exo1-mediated resection of DNA double-strand break ends generates 3′ single-stranded DNA overhangs required for homology-based DNA repair and activation of the ATR-dependent checkpoint. Despite its critical importance in inducing the overall DNA damage response, the mechanisms and regulation of the Exo1 resection pathway remain incompletely understood. Here, we identify the ring-shaped DNA clamp PCNA as a new factor in the Exo1 resection pathway. Using mammalian cells, Xenopus nuclear extracts and purified proteins, we show that after DNA damage, PCNA loads onto double-strand breaks and promotes Exo1 damage association through direct interaction with Exo1. By tethering Exo1 to the DNA substrate, PCNA confers processivity to Exo1 in resection. This role of PCNA in DNA resection is analogous to its function in DNA replication where PCNA serves as a processivity co-factor for DNA polymerases.This publication has 75 references indexed in Scilit:
- Exo1 plays a major role in DNA end resection in humans and influences double-strand break repair and damage signaling decisionsDNA Repair, 2012
- Structures of Human Exonuclease 1 DNA Complexes Suggest a Unified Mechanism for Nuclease FamilyCell, 2011
- The DNA Damage Response: Making It Safe to Play with KnivesMolecular Cell, 2010
- Ku prevents Exo1 and Sgs1-dependent resection of DNA ends in the absence of a functional MRX complex or Sae2The EMBO Journal, 2010
- CtIP Links DNA Double-Strand Break Sensing to ResectionMolecular Cell, 2009
- PCNA Is Required for Initiation of Recombination-Associated DNA Synthesis by DNA Polymerase δMolecular Cell, 2009
- DNA end resection: Many nucleases make light workDNA Repair, 2009
- Single-Stranded DNA Orchestrates an ATM-to-ATR Switch at DNA BreaksMolecular Cell, 2009
- Sgs1 Helicase and Two Nucleases Dna2 and Exo1 Resect DNA Double-Strand Break EndsCell, 2008
- Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage responseThe EMBO Journal, 2008