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Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity

التفاصيل البيبلوغرافية
العنوان: Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity
المؤلفون: Coloma, Javier, Gonzalez-Rodriguez, Nayim, Balaguer, Francisco de Asís, Gmurczyk, Karolina, Aicart-Ramos, Clara, Nuero, Óscar M., Luque-Ortega, Juan Román, Calugaru, Kimberly, Lue, Neal F., Moreno-Herrero, Fernando, Llorca, Óscar
المساهمون: Agencia Estatal de Investigación (España), Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Instituto de Salud Carlos III, Boehringer Ingelheim Fonds, National Institutes of Health (US), European Commission
بيانات النشر: Oxford University Press
سنة النشر: 2023
المجموعة: Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council)
الوصف: The CST complex is a key player in telomere replication and stability, which in yeast comprises Cdc13, Stn1 and Ten1. While Stn1 and Ten1 are very well conserved across species, Cdc13 does not resemble its mammalian counterpart CTC1 either in sequence or domain organization, and Cdc13 but not CTC1 displays functions independently of the rest of CST. Whereas the structures of human CTC1 and CST have been determined, the molecular organization of Cdc13 remains poorly understood. Here, we dissect the molecular architecture of Candida glabrata Cdc13 and show how it regulates binding to telomeric sequences. Cdc13 forms dimers through the interaction between OB-fold 2 (OB2) domains. Dimerization stimulates binding of OB3 to telomeric sequences, resulting in the unfolding of ssDNA secondary structure. Once bound to DNA, Cdc13 prevents the refolding of ssDNA by mechanisms involving all domains. OB1 also oligomerizes, inducing higher-order complexes of Cdc13 in vitro. OB1 truncation disrupts these complexes, affects ssDNA unfolding and reduces telomere length in C. glabrata. Together, our results reveal the molecular organization of C. glabrata Cdc13 and how this regulates the binding and the structure of DNA, and suggest that yeast species evolved distinct architectures of Cdc13 that share some common principles. ; Agencia Estatal de Investigacion [AEI/10.13039/5011000 ´ 11 033]; Ministerio de Ciencia e Innovacion, and co-´ funded by the European Regional Development Fund(ERDF-UE) [PID2020-114429RB-I00 to O.L., PID2020-112998GB-100 to F.M.-H]; Autonomous Region of Madrid and co-funded by the European Social Fund and the European Regional Development Fund [Y2018/BIO4747 and P2018/NMT4443 to O.L. and F.M.-H.]; National Institute of Health Carlos III to CNIO; J.R.L.O. and O.N. acknowledge support from the Molecular Interactions Facility at the CIB-CSIC; N.G.-R. was supported by a Boehringer Ingelheim Fonds PhD fellowship; N.F.L. is funded by NIH [GM107287]. Funding for open access charge: Agencia Estatal de Investigacion ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 0305-1048
1362-4962
Relation: #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114429RB-I00/ES/BASES ESTRUCTURALES Y MOLECULARES DEL ENSAMBLAJE Y ACTIVACION DEL COMPLEJO MTORC1 POR EL SISTEMA CHAPERONA R2TP-HSP90 /; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-112998GB-I00/ES/NUEVAS ESTRATEGIAS BIOFISICAS PARA DESCIFRAR EL PAPEL DE PARB Y DE LA CONDENSINA EN CONDENSACION Y SEGREGACION DEL CROMOSOMA/; Y2018/BIO-4747; P2018/NMT-4443; Publisher's version; https://doi.org/10.1093/nar/gkac1261; Sí; Nucleic Acids Research: gkac1261 (2023); http://hdl.handle.net/10261/287103; http://dx.doi.org/10.13039/501100011033; http://dx.doi.org/10.13039/501100001645; http://dx.doi.org/10.13039/100012818; http://dx.doi.org/10.13039/501100000780; http://dx.doi.org/10.13039/501100004587; http://dx.doi.org/10.13039/501100004837; http://dx.doi.org/10.13039/100000002
DOI: 10.1093/nar/gkac1261
DOI: 10.13039/501100011033
DOI: 10.13039/501100001645
DOI: 10.13039/100012818
DOI: 10.13039/501100000780
DOI: 10.13039/501100004587
DOI: 10.13039/501100004837
DOI: 10.13039/100000002
الاتاحة: http://hdl.handle.net/10261/287103
https://doi.org/10.1093/nar/gkac1261
https://doi.org/10.13039/501100011033
https://doi.org/10.13039/501100001645
https://doi.org/10.13039/100012818
https://doi.org/10.13039/501100000780
https://doi.org/10.13039/501100004587
https://doi.org/10.13039/501100004837
https://doi.org/10.13039/100000002
Rights: open
رقم الانضمام: edsbas.ABDC5520
قاعدة البيانات: BASE
الوصف
تدمد:03051048
13624962
DOI:10.1093/nar/gkac1261