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RTEL1 and MCM10 overcome topological stress during vertebrate replication termination

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 hel...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432576/
https://www.ncbi.nlm.nih.gov/pubmed/36807139
http://dx.doi.org/10.1016/j.celrep.2023.112109
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author 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.
author_facet 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.
author_sort Campos, Lillian V.
collection PubMed
description 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.
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spelling pubmed-104325762023-10-23 RTEL1 and MCM10 overcome topological stress during vertebrate replication termination 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. Cell Rep Article 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. 2023-02-28 2023-02-17 /pmc/articles/PMC10432576/ /pubmed/36807139 http://dx.doi.org/10.1016/j.celrep.2023.112109 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
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.
RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title_full RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title_fullStr RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title_full_unstemmed RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title_short RTEL1 and MCM10 overcome topological stress during vertebrate replication termination
title_sort rtel1 and mcm10 overcome topological stress during vertebrate replication termination
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432576/
https://www.ncbi.nlm.nih.gov/pubmed/36807139
http://dx.doi.org/10.1016/j.celrep.2023.112109
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