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Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication

It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions...

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Autores principales: Kishkevich, Anastasiya, Tamang, Sanjeeta, Nguyen, Michael O., Oehler, Judith, Bulmaga, Elena, Andreadis, Christos, Morrow, Carl A., Jalan, Manisha, Osman, Fekret, Whitby, Matthew C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701231/
https://www.ncbi.nlm.nih.gov/pubmed/36435847
http://dx.doi.org/10.1038/s41467-022-35060-4
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author Kishkevich, Anastasiya
Tamang, Sanjeeta
Nguyen, Michael O.
Oehler, Judith
Bulmaga, Elena
Andreadis, Christos
Morrow, Carl A.
Jalan, Manisha
Osman, Fekret
Whitby, Matthew C.
author_facet Kishkevich, Anastasiya
Tamang, Sanjeeta
Nguyen, Michael O.
Oehler, Judith
Bulmaga, Elena
Andreadis, Christos
Morrow, Carl A.
Jalan, Manisha
Osman, Fekret
Whitby, Matthew C.
author_sort Kishkevich, Anastasiya
collection PubMed
description It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions from a relatively accurate initiation phase to a less accurate elongation phase characterised by extensive template switching between homologous, homeologous and microhomologous DNA sequences. Using an experimental system in fission yeast, where fork collapse is triggered by a site-specific replication barrier, we show that ectopic recombination, associated with the initiation of recombination-dependent replication (RDR), is driven mainly by the Rad51 recombinase, whereas template switching, during the elongation phase of RDR, relies more on DNA annealing by Rad52. This finding provides both evidence and a mechanistic basis for the transition hypothesis.
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spelling pubmed-97012312022-11-28 Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication Kishkevich, Anastasiya Tamang, Sanjeeta Nguyen, Michael O. Oehler, Judith Bulmaga, Elena Andreadis, Christos Morrow, Carl A. Jalan, Manisha Osman, Fekret Whitby, Matthew C. Nat Commun Article It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions from a relatively accurate initiation phase to a less accurate elongation phase characterised by extensive template switching between homologous, homeologous and microhomologous DNA sequences. Using an experimental system in fission yeast, where fork collapse is triggered by a site-specific replication barrier, we show that ectopic recombination, associated with the initiation of recombination-dependent replication (RDR), is driven mainly by the Rad51 recombinase, whereas template switching, during the elongation phase of RDR, relies more on DNA annealing by Rad52. This finding provides both evidence and a mechanistic basis for the transition hypothesis. Nature Publishing Group UK 2022-11-26 /pmc/articles/PMC9701231/ /pubmed/36435847 http://dx.doi.org/10.1038/s41467-022-35060-4 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kishkevich, Anastasiya
Tamang, Sanjeeta
Nguyen, Michael O.
Oehler, Judith
Bulmaga, Elena
Andreadis, Christos
Morrow, Carl A.
Jalan, Manisha
Osman, Fekret
Whitby, Matthew C.
Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title_full Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title_fullStr Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title_full_unstemmed Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title_short Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
title_sort rad52’s dna annealing activity drives template switching associated with restarted dna replication
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9701231/
https://www.ncbi.nlm.nih.gov/pubmed/36435847
http://dx.doi.org/10.1038/s41467-022-35060-4
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