Replication fork instability and the consequences of fork collisions from rereplication

Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stall...

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Main Authors: Orr-Weaver, Terry, Alexander, Jessica Lynne
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Cold Spring Harbor Laboratory Press 2017
Online Access:http://hdl.handle.net/1721.1/108199
https://orcid.org/0000-0002-7934-111X
https://orcid.org/0000-0003-4643-2282
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author Orr-Weaver, Terry
Alexander, Jessica Lynne
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Orr-Weaver, Terry
Alexander, Jessica Lynne
author_sort Orr-Weaver, Terry
collection MIT
description Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA. Current evidence suggests that multiple mechanisms are used to repair rereplication damage, yet these can have deleterious consequences for genome integrity.
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spelling mit-1721.1/1081992022-09-30T11:25:27Z Replication fork instability and the consequences of fork collisions from rereplication Orr-Weaver, Terry Alexander, Jessica Lynne Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Orr-Weaver, Terry Alexander, Jessica Lynne Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA. Current evidence suggests that multiple mechanisms are used to repair rereplication damage, yet these can have deleterious consequences for genome integrity. United States. National Institutes of Health (GM57960) United States. National Institutes of Health (118098) 2017-04-14T22:55:48Z 2017-04-14T22:55:48Z 2016-10 2016-10 Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/108199 Alexander, Jessica L., and Terry L. Orr-Weaver. “Replication Fork Instability and the Consequences of Fork Collisions from Rereplication.” Genes & Development 30, no. 20 (October 15, 2016): 2241–2252. https://orcid.org/0000-0002-7934-111X https://orcid.org/0000-0003-4643-2282 en_US http://dx.doi.org/10.1101/gad.288142.116 Genes & Development Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Cold Spring Harbor Laboratory Press Cold Spring Harbor Laboratory Press
spellingShingle Orr-Weaver, Terry
Alexander, Jessica Lynne
Replication fork instability and the consequences of fork collisions from rereplication
title Replication fork instability and the consequences of fork collisions from rereplication
title_full Replication fork instability and the consequences of fork collisions from rereplication
title_fullStr Replication fork instability and the consequences of fork collisions from rereplication
title_full_unstemmed Replication fork instability and the consequences of fork collisions from rereplication
title_short Replication fork instability and the consequences of fork collisions from rereplication
title_sort replication fork instability and the consequences of fork collisions from rereplication
url http://hdl.handle.net/1721.1/108199
https://orcid.org/0000-0002-7934-111X
https://orcid.org/0000-0003-4643-2282
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