The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence

Detalhes bibliográficos
Autor(a) principal: Li, Shijun
Data de Publicação: 2015
Outros Autores: Tan, Min, Juillard, Franceline, Ponnusamy, Rajesh, Correia, Bruno, Simas, J Pedro, Carrondo, Maria A., McVey, Colin E., Kaye, Kenneth M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/51123
Resumo: © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
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spelling The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistenceDNA virusesKaposi sarcoma-associated herpesvirus (KSHV)CancerEpisomeHerpesvirusLatency-associated nuclear antigen (LANA)Site-directed mutagenesisStructure-functionTumor virusViral protein© 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes.ElsevierRepositório da Universidade de LisboaLi, ShijunTan, MinJuillard, FrancelinePonnusamy, RajeshCorreia, BrunoSimas, J PedroCarrondo, Maria A.McVey, Colin E.Kaye, Kenneth M.2022-02-04T15:07:56Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51123engJ Biol Chem. 2015 Nov 20;290(47):28084-280960021-925810.1074/jbc.M115.6746221083-351Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:38Zoai:repositorio.ul.pt:10451/51123Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:26.568332Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
title The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
spellingShingle The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
Li, Shijun
DNA viruses
Kaposi sarcoma-associated herpesvirus (KSHV)
Cancer
Episome
Herpesvirus
Latency-associated nuclear antigen (LANA)
Site-directed mutagenesis
Structure-function
Tumor virus
Viral protein
title_short The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
title_full The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
title_fullStr The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
title_full_unstemmed The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
title_sort The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding domain dorsal positive electrostatic patch facilitates DNA replication and episome persistence
author Li, Shijun
author_facet Li, Shijun
Tan, Min
Juillard, Franceline
Ponnusamy, Rajesh
Correia, Bruno
Simas, J Pedro
Carrondo, Maria A.
McVey, Colin E.
Kaye, Kenneth M.
author_role author
author2 Tan, Min
Juillard, Franceline
Ponnusamy, Rajesh
Correia, Bruno
Simas, J Pedro
Carrondo, Maria A.
McVey, Colin E.
Kaye, Kenneth M.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Li, Shijun
Tan, Min
Juillard, Franceline
Ponnusamy, Rajesh
Correia, Bruno
Simas, J Pedro
Carrondo, Maria A.
McVey, Colin E.
Kaye, Kenneth M.
dc.subject.por.fl_str_mv DNA viruses
Kaposi sarcoma-associated herpesvirus (KSHV)
Cancer
Episome
Herpesvirus
Latency-associated nuclear antigen (LANA)
Site-directed mutagenesis
Structure-function
Tumor virus
Viral protein
topic DNA viruses
Kaposi sarcoma-associated herpesvirus (KSHV)
Cancer
Episome
Herpesvirus
Latency-associated nuclear antigen (LANA)
Site-directed mutagenesis
Structure-function
Tumor virus
Viral protein
description © 2015 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01T00:00:00Z
2022-02-04T15:07:56Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/51123
url http://hdl.handle.net/10451/51123
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv J Biol Chem. 2015 Nov 20;290(47):28084-28096
0021-9258
10.1074/jbc.M115.674622
1083-351X
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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