PRINCIPAL INVESTIGATOR

Postdoctoral Collaborating Researchers:

• Elisa Cabrera Afonso, PhD (Postdoctoral researcher, Fundación Bioavance contract: Study of genomic instability involving ubiquitin hydrolases – “Estudios de inestabilidad genómica que implican ubiquitin hidrolasas”)
• Juan Ramón Hernández Fernaud, PhD (Postdoctoral researcher, contracted Asociación Española Contra el Cancer/FIISC: Role of UPR in DNA replication control – “Papel de la UPR en el control de la replicación del ADN”)

PhD students and trainees:

• Esperanza Hernández Carralero (Role of Ubiquitin hydrolases in DNA replication control – Papel de Ubiquitin hidrolasas en el control de la replicación del ADN. The Canary Islands Agency of Research, Innovation and Information Sciences, ACIISI)

Research Lines:

• Study of new proteins controlling replication in human cells
• Study of the expression of replication proteins in cancer
• Determination of ubiquitin hydrolases involved in genomic instability in human cells

Funded projects:

• Regulation of the cellular response to DNA damage and replicative stress: the molecular mechanism and implications for tumorigenesis (SAF2016-80626-R “Regulación de la respuesta celular al daño del DNA y al estrés replicativo: Mecanismos moleculares e implicaciones en tumorigenesis”). PIs: Raimundo Freire, Veronique Smits. Ministry of Economy and Competitiveness, MINECO (2017-2019; extended until October 2020, 229,900 €).

Publications 2019:

• Smits VAJ, Cabrera E, Freire R, Gillespie DA. Claspin – checkpoint adaptor and DNA replication factor. FEBS J. 2019 Feb;286(3):441-455. doi: 10.1111/febs.14594
• Herruzo E,Santos B,Freire R,Carballo JA,San-Segundo PA.Characterization of Pch2 localization determinants reveals a nucleolar-independent role in the meiotic recombination checkpoint. 2019 Sep;128(3):297-316. doi:10.1007/s00412-019-00696-7
• Cabrera E, Raninga P, Khanna K, Freire R. GSK3-β stimulates claspin degradation via β-TrCP ubiquitin ligase and alters cancer cell survival. Cancers (Basel). 2019 Jul 29;11(8). doi: 10.3390/cancers11081073
• Singh AN, Oehler J, Torrecilla I, Kilgas S, Li S, Vaz B, Guérillon C, Fielden J, Hernandez-Carralero E, Cabrera E, Tullis ID, Meerang M, Barber PR, Freire R, Parsons J, Vojnovic B, Kiltie AE, Mailand N, Ramadan K. The p97-Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8. EMBO J. 2019 Oct 4;38(21):e102361. doi: 10.15252/embj.2019102361.

Other Selected publications from the last 10 years:

• Cabrera E, Hernández-Pérez S, Koundrioukoff S, Debatisse M, Kim D, Smolka MB, Freire R, Gillespie DA. PERK inhibits DNA replication during the Unfolded Protein Response via Claspin and Chk1. Oncogene. 2017 Feb 2;36(5):678-686. doi:10.1038/onc.2016.239
• Hernandez-Perez S, Cabrera E, Salido E, Lim M, Reid L, Lakhani SR, Khanna KK, Saunus JM, Freire R. DUB3 and USP7 de-ubquitination enzymes control replication inhibitor Geminin: molecular characterization and association with breast cancer. Oncogene. 2017 Aug 17;36(33):4802-4809. doi: 10.1038/onc.2017.21
• Hernandez-Perez S, Cabrera E, Amoedo H, Rodriguez-Acebes S, Koundrioukoff S, Debatisse M, Mendez J, Freire R. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Mol Oncol. 2016 Oct;10(8):1196-206. doi:10.1016/j.molonc.2016.05.008
• Martín Y, Cabrera E, Amoedo H, Hernández-Pérez S, Domínguez-Kelly R, Freire R. USP29 controls the stability of checkpoint adaptor Claspin by deubiquitination. Oncogene. 2015 Feb 19;34(8):1058-63. doi: 10.1038/onc.2014.38
• Domínguez-Kelly R, Martín Y, Koundrioukoff S, Tanenbaum ME, Smits VA, Medema RH, Debatisse M, Freire R. Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. J Cell Biol. 2011 Aug 22;194(4):567-79. doi: 10.1083/jcb.201101047