The DNA Single-Strand Break Repair Machinery Facilitates CAF-1-Mediated Histone Deposition at Oxidative DNA Strand Breaks

TL;DR

This study reveals that the DNA single-strand break repair machinery in quiescent human cells facilitates histone H3.1 deposition at oxidative DNA breaks, linking chromatin remodeling to efficient DNA repair.

Contribution

It uncovers a novel role for the DNA single-strand break repair machinery in promoting histone deposition during oxidative DNA damage response.

Findings

Histone H3.1 accumulates at DNA break sites following oxidative stress.

Core SSBR proteins like PARP and XRCC1 are essential for histone deposition.

Depleting CAF-1 slows down DNA repair in quiescent cells.

Abstract

Oxidative DNA single strand breaks arise continuously in cells and defects in their repair have been implicated in neurological disease. While much progress has been made in understanding how chromosomal single strand breaks are repaired little is known about the changes chromatin structure that accompany this process. Here, we show that nascent recombinant histone H3.1 protein accumulates and is deposited into chromatin at sites of DNA strand breakage in quiescent human cells following oxidative stress, and that core components of the single-strand break repair machinery are required for this process. We show that the SSBR sensor and scaffold proteins poly (ADP-ribose) polymerase and XRCC1 facilitate accumulation of chromatin assembly factor-1 (CAF-1) at sites of oxidative DNA strand breakage, which in turn mediates the deposition of Histone H3.1. We also demonstrate that depletion of CAF-1 slows global rates of DNA strand break repair in quiescent cells following oxidative stress, demonstrating that single-strand break repair and histone deposition are tightly coordinated processes. These data describe a novel role for the DNA singlestrand break repair machinery and implicate histone turnover as a core component of the cellular response of quiescent cells to oxidative damage.