Strand asymmetry influences mismatch resolution during a single-strand annealing

Background: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage. Results: Here, we develop a gen...

Descripción completa

Detalles Bibliográficos
Autores: Pokusaeva, Victoria O., Rosado Diez, Aránzuru, Espinar, Lorena, Torelló Pérez, Albert, Filion, Guillaume
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/53341
Acceso en línea:http://hdl.handle.net/10230/53341
http://dx.doi.org/10.1186/s13059-022-02665-3
Access Level:acceso abierto
Palabra clave:Genòmica
Genètica
Embriologia
id ES_32091db4fd4efed4a0d319fa33b4fad2
oai_identifier_str oai:recercat.cat:10230/53341
network_acronym_str ES
network_name_str España
repository_id_str
spelling Strand asymmetry influences mismatch resolution during a single-strand annealingPokusaeva, Victoria O.Rosado Diez, AránzuruEspinar, LorenaTorelló Pérez, AlbertFilion, GuillaumeGenòmicaGenèticaEmbriologiaBackground: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage. Results: Here, we develop a genome-wide assay whereby the same DNA lesion is repaired in different genomic contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated if the break is repaired through single-strand annealing. The resolution of the mismatch showed a 60-80% bias in favor of the strand with the longest 3' flap. The location of the lesion in the genome and the type of mismatch had little influence on the bias. Instead, we observe a complete reversal of the bias when the longest 3' flap is moved to the opposite strand by changing the position of the double-strand break in the reporter. Conclusions: These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during a single-strand annealing.We acknowledge the financial support of the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN-2020-06377), the Spanish Ministry of Economy, Industry and Competitiveness (“Centro de Excelencia Severo Ochoa 2013-2017”, Plan Estatal PGC2018-099807-B-I00), of the CERCA Programme/Generalitat de Catalunya, and of the European Research Council (Synergy Grant 609989). VOP was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie programme (665385). We also acknowledge the support of the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnershipBioMed Central202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/53341http://dx.doi.org/10.1186/s13059-022-02665-3reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/EC/H2020/665385info:eu-repo/grantAgreement/EC/FP7/609989© Victoria O. Pokusaeva et al. 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 licence, and indicate if changes were madehttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/533412026-05-29T05:05:01Z
dc.title.none.fl_str_mv Strand asymmetry influences mismatch resolution during a single-strand annealing
title Strand asymmetry influences mismatch resolution during a single-strand annealing
spellingShingle Strand asymmetry influences mismatch resolution during a single-strand annealing
Pokusaeva, Victoria O.
Genòmica
Genètica
Embriologia
title_short Strand asymmetry influences mismatch resolution during a single-strand annealing
title_full Strand asymmetry influences mismatch resolution during a single-strand annealing
title_fullStr Strand asymmetry influences mismatch resolution during a single-strand annealing
title_full_unstemmed Strand asymmetry influences mismatch resolution during a single-strand annealing
title_sort Strand asymmetry influences mismatch resolution during a single-strand annealing
dc.creator.none.fl_str_mv Pokusaeva, Victoria O.
Rosado Diez, Aránzuru
Espinar, Lorena
Torelló Pérez, Albert
Filion, Guillaume
author Pokusaeva, Victoria O.
author_facet Pokusaeva, Victoria O.
Rosado Diez, Aránzuru
Espinar, Lorena
Torelló Pérez, Albert
Filion, Guillaume
author_role author
author2 Rosado Diez, Aránzuru
Espinar, Lorena
Torelló Pérez, Albert
Filion, Guillaume
author2_role author
author
author
author
dc.subject.none.fl_str_mv Genòmica
Genètica
Embriologia
topic Genòmica
Genètica
Embriologia
description Background: Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. The molecular mechanisms of those biases are still poorly understood because it is difficult to isolate the contributions of DNA repair from those of DNA damage. Results: Here, we develop a genome-wide assay whereby the same DNA lesion is repaired in different genomic contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated if the break is repaired through single-strand annealing. The resolution of the mismatch showed a 60-80% bias in favor of the strand with the longest 3' flap. The location of the lesion in the genome and the type of mismatch had little influence on the bias. Instead, we observe a complete reversal of the bias when the longest 3' flap is moved to the opposite strand by changing the position of the double-strand break in the reporter. Conclusions: These results suggest that the processing of the double-strand break has a major influence on the repair of mismatches during a single-strand annealing.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/53341
http://dx.doi.org/10.1186/s13059-022-02665-3
url http://hdl.handle.net/10230/53341
http://dx.doi.org/10.1186/s13059-022-02665-3
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/665385
info:eu-repo/grantAgreement/EC/FP7/609989
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405650055856128
score 15,812455

Similares en LA Referencia