SUMO2 conjugation of PCNA facilitates chromatin remodeling to resolve transcription-replication conflicts

Nature Communications
Min LiYilun Liu

Abstract

During DNA synthesis, DNA replication and transcription machinery can collide, and the replication fork may temporarily dislodge RNA polymerase II (RNAPII) to resolve the transcription-replication conflict (TRC), a major source of endogenous DNA double-strand breaks (DSBs) and common fragile site (CFS) instability. However, the mechanism of TRC resolution remains unclear. Here, we show that conjugation of SUMO2, but not SUMO1 or SUMO3, to the essential replication factor PCNA is induced on transcribed chromatin by the RNAPII-bound helicase RECQ5. Proteomic analysis reveals that SUMO2-PCNA enriches histone chaperones CAF1 and FACT in the replication complex via interactions with their SUMO-interacting motifs. SUMO2-PCNA enhances CAF1-dependent histone deposition, which correlates with increased histone H3.1 at CFSs and repressive histone marks in the chromatin to reduce chromatin accessibility. Hence, SUMO2-PCNA dislodges RNAPII at CFSs, and overexpressing either SUMO2-PCNA or CAF1 reduces the incidence of DSBs in TRC-prone RECQ5-deficient cells.

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Citations

May 28, 2019·Genes & Development·Belén Gómez-González, Andrés Aguilera
Sep 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Min LiYilun Liu
Dec 14, 2018·Genes·Louis-Alexandre FournierPeter C Stirling
Jun 12, 2020·Frontiers in Cell and Developmental Biology·Zeid Hamadeh, Peter Lansdorp
Oct 24, 2020·Essays in Biochemistry·Joseph A Newman, Opher Gileadi
Jan 12, 2021·Current Genetics·Nafees AhamadYong-Jie Xu
Feb 11, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mathias BoulangerGuillaume Bossis
Aug 20, 2021·Frontiers in Genetics·Amira Elbakry, Markus Löbrich
Aug 28, 2021·Biomolecules·Commodore St GermainJacqueline H Barlow
Sep 23, 2021·Experimental & Molecular Medicine·Seo Yun LeeKyle M Miller
Nov 26, 2021·Biochemical Society Transactions·Aleix Bayona-Feliu, Andrés Aguilera

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Methods Mentioned

BETA
flow cytometry
ubiquitination
electrophoresis
transfection
immunoprecipitation
ChIP
co-immunoprecipitation
pull-down
pull-downs
immunodepletion

Software Mentioned

Comet Score

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