Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions

The histone demethylase KDM5A erases histone H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of KDM5A have been identified, how KDM5A recognizes DNA lesion sites within chromatin is unknown. Here, we identify two factors that act upstr...

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Autores: Kumbhar, Ramhari, Sanchez, Anthony, Perren, Jullian, Gong, Fade, Corujo, David|||0000-0001-7930-0935, Medina, Frank, Devanathan, Sravan K., Xhemalce, Blerta, Matouschek, Andreas, Buschbeck, Marcus|||0000-0002-3218-4567, Buck-Koehntop, Bethany A., Miller, Kyle M.
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270500
Acceso en línea:https://ddd.uab.cat/record/270500
https://dx.doi.org/urn:doi:10.1083/jcb.202006149
Access Level:acceso abierto
Palabra clave:Chromatin
DNA
DNA Breaks, Double-Stranded
DNA Damage
Histones
Humans
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Recombinational DNA Repair
Retinoblastoma-Binding Protein 2
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spelling Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesionsKumbhar, RamhariSanchez, AnthonyPerren, JullianGong, FadeCorujo, David|||0000-0001-7930-0935Medina, FrankDevanathan, Sravan K.Xhemalce, BlertaMatouschek, AndreasBuschbeck, Marcus|||0000-0002-3218-4567Buck-Koehntop, Bethany A.Miller, Kyle M.ChromatinDNADNA Breaks, Double-StrandedDNA DamageHistonesHumansPoly Adenosine Diphosphate RibosePoly(ADP-ribose) PolymerasesRecombinational DNA RepairRetinoblastoma-Binding Protein 2The histone demethylase KDM5A erases histone H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of KDM5A have been identified, how KDM5A recognizes DNA lesion sites within chromatin is unknown. Here, we identify two factors that act upstream of KDM5A to promote its association with DNA damage sites. We have identified a noncanonical poly(ADP-ribose) (PAR)-binding region unique to KDM5A. Loss of the PARbinding region or treatment with PAR polymerase (PARP) inhibitors (PARPi's) blocks KDM5A-PAR interactions and DNA repair functions of KDM5A. The histone variant macroH2A1.2 is also specifically required for KDM5A recruitment and function at DNA damage sites, including homology-directed repair of DNA double-strand breaks and repression of transcription at DNA breaks. Overall, this work reveals the importance of PAR binding and macroH2A1.2 in KDM5A recognition of DNA lesion sites that drive transcriptional and repair activities at DNA breaks within chromatin that are essential for maintaining genome integrityUniversitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/270500https://dx.doi.org/urn:doi:10.1083/jcb.202006149reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE16/00011Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094005-B-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2705002026-06-06T12:50:31Z
dc.title.none.fl_str_mv Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
title Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
spellingShingle Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
Kumbhar, Ramhari
Chromatin
DNA
DNA Breaks, Double-Stranded
DNA Damage
Histones
Humans
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Recombinational DNA Repair
Retinoblastoma-Binding Protein 2
title_short Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
title_full Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
title_fullStr Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
title_full_unstemmed Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
title_sort Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
dc.creator.none.fl_str_mv Kumbhar, Ramhari
Sanchez, Anthony
Perren, Jullian
Gong, Fade
Corujo, David|||0000-0001-7930-0935
Medina, Frank
Devanathan, Sravan K.
Xhemalce, Blerta
Matouschek, Andreas
Buschbeck, Marcus|||0000-0002-3218-4567
Buck-Koehntop, Bethany A.
Miller, Kyle M.
author Kumbhar, Ramhari
author_facet Kumbhar, Ramhari
Sanchez, Anthony
Perren, Jullian
Gong, Fade
Corujo, David|||0000-0001-7930-0935
Medina, Frank
Devanathan, Sravan K.
Xhemalce, Blerta
Matouschek, Andreas
Buschbeck, Marcus|||0000-0002-3218-4567
Buck-Koehntop, Bethany A.
Miller, Kyle M.
author_role author
author2 Sanchez, Anthony
Perren, Jullian
Gong, Fade
Corujo, David|||0000-0001-7930-0935
Medina, Frank
Devanathan, Sravan K.
Xhemalce, Blerta
Matouschek, Andreas
Buschbeck, Marcus|||0000-0002-3218-4567
Buck-Koehntop, Bethany A.
Miller, Kyle M.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Chromatin
DNA
DNA Breaks, Double-Stranded
DNA Damage
Histones
Humans
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Recombinational DNA Repair
Retinoblastoma-Binding Protein 2
topic Chromatin
DNA
DNA Breaks, Double-Stranded
DNA Damage
Histones
Humans
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Recombinational DNA Repair
Retinoblastoma-Binding Protein 2
description The histone demethylase KDM5A erases histone H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of KDM5A have been identified, how KDM5A recognizes DNA lesion sites within chromatin is unknown. Here, we identify two factors that act upstream of KDM5A to promote its association with DNA damage sites. We have identified a noncanonical poly(ADP-ribose) (PAR)-binding region unique to KDM5A. Loss of the PARbinding region or treatment with PAR polymerase (PARP) inhibitors (PARPi's) blocks KDM5A-PAR interactions and DNA repair functions of KDM5A. The histone variant macroH2A1.2 is also specifically required for KDM5A recruitment and function at DNA damage sites, including homology-directed repair of DNA double-strand breaks and repression of transcription at DNA breaks. Overall, this work reveals the importance of PAR binding and macroH2A1.2 in KDM5A recognition of DNA lesion sites that drive transcriptional and repair activities at DNA breaks within chromatin that are essential for maintaining genome integrity
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/270500
https://dx.doi.org/urn:doi:10.1083/jcb.202006149
url https://ddd.uab.cat/record/270500
https://dx.doi.org/urn:doi:10.1083/jcb.202006149
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PIE16/00011
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094005-B-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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