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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Cold Spring Harbor Laboratory Press
2017
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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. |
first_indexed | 2024-09-23T08:48:38Z |
format | Article |
id | mit-1721.1/108199 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T08:48:38Z |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
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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 |
work_keys_str_mv | AT orrweaverterry replicationforkinstabilityandtheconsequencesofforkcollisionsfromrereplication AT alexanderjessicalynne replicationforkinstabilityandtheconsequencesofforkcollisionsfromrereplication |