RTEL1 Suppresses G-quadruplex-associated R-loops at Difficult-to-replicate Loci in the Human Genome

Overview

Journal Nat Struct Mol Biol

Specialties Cell Biology
Molecular Biology

Date 2020 May 14

PMID 32398827

Citations 45

Authors

Wei Wu

Rahul Bhowmick

Ivan Vogel

Ozgun Ozer

Fiorella Ghisays

Roshan S Thakur

Esther Sanchez de Leon

Philipp H Richter

Liqun Ren

John H Petrini

Ian D Hickson

Ying Liu

Affiliations

Soon will be listed here.

Abstract

Oncogene activation during tumorigenesis generates DNA replication stress, a known driver of genome rearrangements. In response to replication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated during interphase and subsequently complete locus duplication in mitosis in a process known as 'MiDAS'. Here, we demonstrate that RTEL1 (regulator of telomere elongation helicase 1) has a genome-wide role in MiDAS at loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase function. We reveal that SLX4 is required for the timely recruitment of RTEL1 to the affected loci, which in turn facilitates recruitment of other proteins required for MiDAS, including RAD52 and POLD3. Our findings demonstrate that RTEL1 is required for MiDAS and suggest that RTEL1 maintains genome stability by resolving conflicts that can arise between the replication and transcription machineries.

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