Checkpoint response to DNA damage and human deseases
PRINCIPAL INVESTIGATOR
Veronique Smits PhD
Contracted investigator SCS/FIISC, HUC Research Unit |
POSTDOCTORAL RESEARCHERS:
- David Gillespie, PhD (Contracted investigator, Agustín de Betancourt programme, ULL)
PHD STUDENTS AND TRAINEES:
- Ignacio Alonso de Vega (Health Sciences Doctoral Programme, The Canary Islands Agency of Research, Innovation and Information Sciences, ACIISI)
- Yeray Hernández Reyes (Health Sciences Doctoral Programme, The Canary Islands Health Research Foundation, FIISC. Project SAF2016-80626-R)
TECHNICAL AND ADMINISTRATIVE STAFF:
- Cristina Paz Cabrera
RESEARCH LINES:
We study the cellular mechanisms of the response to DNA damage, specifically post-translational modifications like the ubiquitination, SUMOylation and acetylation of proteins in these pathways, and of histones. These modifications seem to be crucial to relax the chromatin structure, and to allow DNA damage to be identified and repaired by DNA damage response proteins. We intend to identify new proteins regulating chromatin modifying enzymes in order to reveal their role in the cellular response to DNA damage.
FUNDED PROJECTS:
- Regulation of the cellular response to DNA damage and replicative stress: molecular mechanisms and the role of tumorigeneses (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, 229,900 €).
- Dynamics and chromosome stability (BFU2017-90889-REDT “Networks of Excellence”). PI: Veronique Smits (Network coordinator: Felix Prado). Ministry of Economy and Competitiveness, MINECO (2018-2019, 10,000 €)
- Study of the sensitivity of ovarian cancer cells to chemotherapy by the control of PHF2 (PIFUN 16/18). IP: Veronique Smits. FIISC (2019-2020, 19,314.34 €)
- In vivo screening based on the reversal of cellular phenotypes to find new drugs that inhibit the Chk1 kinase involved in cancer. Project Agustín de Betancourt “Rastreo in vivo basado en la reversión de fenotipo celular para encontrar nuevos fármacos inhibidores contra la quinasa Chk1 implicada en cáncer”. PI: David Gillespie; Supervisor: Eduardo Salido Ruiz. Tenerife regional Government (2017-2021, 160,000 €).
PUBLICATIONS IN 2019:
- Alonso-de Vega I, Paz-Cabrera MC, Wiegant WW, Checa-Rodríguez C, Huertas P, Freire R, van Attikum H, Smits VAJ. PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks. BioRxiv, 2019. doi:1101/782490
- Sinha D, Nag P, Nanayakkara D, Duijf PHG, Burgess A, Raninga P, Smits VAJ, Bain AL, Subramanian G, Wall M, Finnie JW, Kalimutho M, Khanna KK. Cep55 overexpression promotes genomic instability and tumorigenesis in mice. BioRxiv, 2019. doi: 10.1101/780775
- Smits VAJ, Cabrera E, Freire R, Gillespie DA (2019). Claspin – checkpoint adaptor and DNA replication factor. FEBS J. 2019 Feb;286(3):441-455. doi: 10.1111/febs.14594
OTHER SELECTED PUBLICATIONS FROM THE LAST 10 YEARS:
- Smits VAJ, Gillespie DA. DNA damage control: regulation and functions of checkpoint kinase 1. FEBS J. 2015 Oct;282(19):3681-92. doi: 10.1111/febs.13387
- Delgado-Díaz MR, Martín Y, Berg A, Freire R, Smits VAJ. Dub3 controls DNA damage signalling by direct deubiquitination of H2AX. Mol. Oncol. 2014 Jul;8(5):884-93. doi: 10.1016/j.molonc.2014.03.003
- Alonso de Vega I, Martín Y, Smits VAJ. USP7 controls Chk1 protein stability by direct deubiquitination. Cell Cycle. 2014;13(24):3921-6. doi: 10.4161/15384101.2014.973324
- Warmerdam DO, Brinkman EK, Marteijn JA, Medema RH, Kanaar R, Smits VA. UV-induced G2 checkpoint depends on p38 MAPK and minimal activation of ATR-Chk1 pathway. J Cell Science. 2013 May 1;126(Pt 9):1923-30. doi: 10.1242/jcs.118265
- Smits VAJ. EDD induces cell cycle arrest by increasing p53 levels. Cell Cycle. 2012 Feb 15;11(4):715-20. doi: 10.4161/cc.11.4.19154