Rpd3L regulates transcription-replication conflict via H3K4 methylation–dependent and –independent chromatin mechanisms
Journal
Science Advances
Journal Volume
12
Journal Issue
24
ISSN
2375-2548
Date Issued
2026-06-12
Author(s)
Abstract
Faithful genome duplication requires coordination between transcription and replication. Disruption of this coordination causes transcription-replication conflicts (TRCs), leading to replication stress and genome instability. How chromatin regulators modulate these processes remains unclear. Here, we show that the Rpd3L histone deacetylase complex dynamically modulates chromatin state to control replication fork progression and buffer TRCs in Saccharomyces cerevisiae. Rpd3L is targeted through both histone H3 lysine 4 methylation-dependent recruitment and methylation-independent mechanisms engaged under replication stress. Loss of H3K4 methylation or Rpd3L function promotes histone acetylation, accelerates fork progression through transcribed regions, and increases transcription-associated genome instability. Balanced acetylation at multiple histone lysines is required to stabilize replication forks under stress. While histone deacetylase complexes have been implicated in repairing damaged forks, our findings reveal that Rpd3L acts preemptively to modulate chromatin state and replication dynamics during TRCs, defining a chromatin-based mechanism that safeguards genome stability. Copyright © 2026 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. distributed under a Creative Commons Attribution nonCommercial license 4.0 (CC BY-nC).
Subjects
Acetylation
Chromatin
DNA Replication
Genomic Instability
Histone Deacetylases
Histones
Lysine
Methylation
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription
Genetic
Publisher
American Association for the Advancement of Science
Description
Article number eadz7842
Type
journal article