Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication
Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/25490 |
| _version_ | 1828380206899920896 |
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| author | Carl A Morrow Michael O Nguyen Andrew Fower Io Nam Wong Fekret Osman Claire Bryer Matthew C Whitby |
| author_facet | Carl A Morrow Michael O Nguyen Andrew Fower Io Nam Wong Fekret Osman Claire Bryer Matthew C Whitby |
| author_sort | Carl A Morrow |
| collection | DOAJ |
| description | Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. Collapsed forks can be rescued by homologous recombination, which restarts replication. However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. Based on our findings, we propose that IFSA is a potential threat to genomic stability in eukaryotes. |
| first_indexed | 2024-12-10T03:53:23Z |
| format | Article |
| id | doaj.art-b8951f8da06942ba86586b4199bd28af |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:53:23Z |
| publishDate | 2017-06-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-b8951f8da06942ba86586b4199bd28af2022-12-22T02:03:11ZengeLife Sciences Publications LtdeLife2050-084X2017-06-01610.7554/eLife.25490Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replicationCarl A Morrow0Michael O Nguyen1Andrew Fower2Io Nam Wong3Fekret Osman4Claire Bryer5Matthew C Whitby6https://orcid.org/0000-0003-0951-3374Department of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomProblems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination. Collapsed forks can be rescued by homologous recombination, which restarts replication. However, replication restart is relatively slow and, therefore, replication termination may frequently occur by an active fork converging on a collapsed fork. We find that this type of non-canonical fork convergence in fission yeast is prone to trigger deletions between repetitive DNA sequences via a mechanism we call Inter-Fork Strand Annealing (IFSA) that depends on the recombination proteins Rad52, Exo1 and Mus81, and is countered by the FANCM-related DNA helicase Fml1. Based on our findings, we propose that IFSA is a potential threat to genomic stability in eukaryotes.https://elifesciences.org/articles/25490DNA replicationhomologous recombinationRad52replication fork collapsereplication fork barrierMus81 |
| spellingShingle | Carl A Morrow Michael O Nguyen Andrew Fower Io Nam Wong Fekret Osman Claire Bryer Matthew C Whitby Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication eLife DNA replication homologous recombination Rad52 replication fork collapse replication fork barrier Mus81 |
| title | Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication |
| title_full | Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication |
| title_fullStr | Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication |
| title_full_unstemmed | Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication |
| title_short | Inter-Fork Strand Annealing causes genomic deletions during the termination of DNA replication |
| title_sort | inter fork strand annealing causes genomic deletions during the termination of dna replication |
| topic | DNA replication homologous recombination Rad52 replication fork collapse replication fork barrier Mus81 |
| url | https://elifesciences.org/articles/25490 |
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