A multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensis

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dc.contributor.authorFernandes, Carlos A.H. [UNESP]
dc.contributor.authorMorea, Edna Gicela O. [UNESP]
dc.contributor.authordos Santos, Gabriel A. [UNESP]
dc.contributor.authorda Silva, Vitor L. [UNESP]
dc.contributor.authorVieira, Marina Roveri [UNESP]
dc.contributor.authorViviescas, Maria Alejandra [UNESP]
dc.contributor.authorChatain, Jean
dc.contributor.authorVadel, Aurélie
dc.contributor.authorSaintomé, Carole
dc.contributor.authorFontes, Marcos Roberto M. [UNESP]
dc.contributor.authorCano, Maria Isabel Nogueira [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionÉcole Normale Supérieure Paris-Saclay
dc.contributor.institutionINSERM U1154
dc.contributor.institutionUFR927
dc.date.accessioned2020-12-12T02:01:06Z
dc.date.available2020-12-12T02:01:06Z
dc.date.issued2020-07-01
dc.description.abstractBackground: Telomeres are chromosome end structures important in the maintenance of genome homeostasis. They are replenished by the action of telomerase and associated proteins, such as the OB (oligonucleotide/oligosaccharide-binding)-fold containing telomere-end binding proteins (TEBP) which plays an essential role in telomere maintenance and protection. The nature of TEBPs is well known in higher and some primitive eukaryotes, but it remains undetermined in trypanosomatids. Previous in silico searches have shown that there are no homologs of the classical TEPBs in trypanosomatids, including Leishmania sp. However, Replication Protein A subunit 1 (RPA-1), an OB-fold containing DNA-binding protein, was found co-localized with trypanosomatids telomeres and showed a high preference for the telomeric G-rich strand. Methods and results: We predicted the absence of structural homologs of OB-fold containing TEBPs in the Leishmania sp. genome using structural comparisons. We demonstrated by molecular docking that the ssDNA binding mode of LaRPA-1 shares features with the higher eukaryotes POT1 and RPA-1 crystal structures ssDNA binding mode. Using fluorescence spectroscopy, protein-DNA interaction assays, and FRET, we respectively show that LaRPA-1 shares some telomeric functions with the classical TEBPs since it can bind at least one telomeric repeat, protect the telomeric G-rich DNA from 3′-5′ Exonuclease I digestion, and unfold telomeric G-quadruplex. Conclusions: Our results suggest that RPA-1 emerges as a TEBP in trypanosomatids, and in this context, we present two possible evolutionary landscapes of trypanosomatids RPA-1 that could reflect upon the evolution of OB-fold containing TEBPs from all eukaryotes.en
dc.description.affiliationDepartment of Biophysics and Pharmacology Biosciences Institute São Paulo State University (UNESP) – Botucatu
dc.description.affiliationLaboratoire de Biologie et Pharmacologie Appliquée École Normale Supérieure Paris-Saclay
dc.description.affiliationDepartment of Chemical and Biological Sciences São Paulo State University (UNESP) – Botucatu
dc.description.affiliationMNHN CNRS UMR 7196 INSERM U1154, 43 rue Cuvier
dc.description.affiliationSorbonne Université UFR927, 4 place Jussieu
dc.description.affiliationUnespDepartment of Biophysics and Pharmacology Biosciences Institute São Paulo State University (UNESP) – Botucatu
dc.description.affiliationUnespDepartment of Chemical and Biological Sciences São Paulo State University (UNESP) – Botucatu
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCentre National de la Recherche Scientifique
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipInstitut National de la Santé et de la Recherche Médicale
dc.description.sponsorshipMuséum National d'Histoire Naturelle
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCAPES: 171895/2018-01
dc.description.sponsorshipIdFAPESP: 2015/17286-0
dc.description.sponsorshipIdFAPESP: 2015/18641-5
dc.description.sponsorshipIdFAPESP: 2018/0395-6
dc.description.sponsorshipIdFAPESP: 2018/04375-2
dc.description.sponsorshipIdFAPESP: 2019/11496-3
dc.description.sponsorshipIdCNPq: 305300/2006-7
dc.description.sponsorshipIdCAPES: 88881
dc.identifierhttp://dx.doi.org/10.1016/j.bbagen.2020.129607
dc.identifier.citationBiochimica et Biophysica Acta - General Subjects, v. 1864, n. 7, 2020.
dc.identifier.doi10.1016/j.bbagen.2020.129607
dc.identifier.issn1872-8006
dc.identifier.issn0304-4165
dc.identifier.scopus2-s2.0-85082711286
dc.identifier.urihttp://hdl.handle.net/11449/200232
dc.language.isoeng
dc.relation.ispartofBiochimica et Biophysica Acta - General Subjects
dc.sourceScopus
dc.subjectG-quadruplex
dc.subjectLeishmania sp.
dc.subjectOB-fold
dc.subjectRPA-1
dc.subjectTelomere end-binding protein
dc.titleA multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensisen
dc.typeArtigo

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