RTEL1 and MCM10 overcome topological stress during vertebrate replication termination.

Autor: Campos LV; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Van Ravenstein SX; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Vontalge EJ; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Greer BH; Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA., Heintzman DR; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., Kavlashvili T; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA., McDonald WH; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA., Rose KL; Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, USA., Eichman BF; Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA., Dewar JM; Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: james.dewar@vanderbilt.edu.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112109. Date of Electronic Publication: 2023 Feb 17.
DOI: 10.1016/j.celrep.2023.112109
Abstrakt: Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, replication forks ultimately overcome fork stalling, suggesting that alternative mechanisms of termination exist. Using proteomics in Xenopus egg extracts, we show that the helicase RTEL1 and the replisome protein MCM10 are highly enriched on chromatin during fork convergence and are crucially important for fork convergence under conditions of topological stress. RTEL1 and MCM10 cooperate to promote fork convergence and do not impact topoisomerase activity but do promote fork progression through a replication barrier. Thus, RTEL1 and MCM10 play a general role in promoting progression of stalled forks, including when forks stall during termination. Our data reveal an alternate mechanism of termination involving RTEL1 and MCM10 that can be used to complete DNA synthesis under conditions of topological stress.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE