RTEL1 and MCM10 overcome topological stress during vertebrate replication termination

• Published in: Cell reports (Cambridge) Vol. 42; no. 2; p. 112109
• Main Authors: Campos, Lillian V., Van Ravenstein, Sabrina X., Vontalge, Emma J., Greer, Briana H., Heintzman, Darren R., Kavlashvili, Tamar, McDonald, W. Hayes, Rose, Kristie Lindsey, Eichman, Brandt F., Dewar, James M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.02.2023; Elsevier
• Subjects: biochemistry; CP: Molecular biology; DNA replication; fork stalling; mass spectrometry; MCM10; replication termination; RTEL1; topoisomerase; Xenopus; Xenopus; DNA replication; RTEL1; fork stalling; biochemistry; CP: Molecular biology; topoisomerase; mass spectrometry; MCM10; replication termination
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.112109

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. [Display omitted] •Proteomic analysis of terminating replication forks identifies RTEL1 and MCM10•Fork stalling during termination is overcome by RTEL1 and MCM10•RTEL1 and MCM10 physically interact and functionally cooperate during termination•Fork stalling prior to termination is also overcome by RTEL1 and MCM10 Topological stress can stall DNA replication forks during the stage of replication termination. Campos et al. find that the helicase RTEL1 and the replication protein MCM10 allow replication forks to overcome stalling during termination. They show that RTEL1 and MCM10 form an alternative mechanism of termination operating under topological stress.