PRINCIPAL INVESTIGATOR

PhD RESEARCHERS

• Jessel Ayra Plasencia, PhD (postdoctoral researcher “Juan de la Cierva – Training”; FIISC, Research Unit, HUC)

DOCTORAL STUDENTS, FELLOWS AND RESEARCHERS IN TRAINING:

• Yeray Hernández Reyes (Doctoral Program in Health Sciences ULL, Canary Islands Foundation Institute of Health Research of the Canary Islands, FIISC. ACIISI Grant, 2018-2023)
• Cintia Fonseca Rodríguez (Doctoral Program in Health Sciences ULL, Canary Islands Foundation Institute of Health Research of the Canary Islands, FIISC. FPI Contract, MICINN, 2021-2025)

TECHNICAL OR MANAGEMENT STAFF

• Cristina Paz Cabrera (Canary Islands Foundation Institute of Health Research of the Canary Islands, FIISC)

LINES OF RESEARCH

The DNA damage response (DDR) detects, signals, and repairs DNA lesions and is essential for maintaining genome integrity and serving as the first line of defense in the early stages of cancer development. Efficient DNA repair requires the correct and timely coordination of a multitude of signaling events, in which post-translational modifications (PTMs) play a fundamental role. Because DNA lesions occur and are repaired within the context of chromatin, chromatin PTMs also influence this process. Together, PTMs function to locally open the chromatin structure, aid in the localization of repair proteins to the sites of DNA damage, and activate kinases that arrest the cell cycle.

Veronique Smits' group studies the mechanistic details of the enzymes that regulate these PTMs, for example ubiquitin hydrolases and chromatin regulators, and their importance in different processes that prevent genomic instability, such as DNA repair and chromatin structure. 

Furthermore, DNA-damaging agents are widely used in cancer treatments due to their toxicity to proliferating cells, and the effectiveness of antitumor treatments is determined by the cells' ability to repair the damage. Therefore, the potential role of these enzymes as a way to modulate cancer treatment is being investigated.

FUNDED PROJECTS

• Post-translational modifications in the control of genome stability and their role in cancer and other pathologies (PID2019-109222RB-I00). IP: Raimundo Freire and Veronique Smits. Ministry of Science and Innovation (06/2020 – 05/2023, €278,300)
• Enzymatic control of genome integrity maintenance: molecular mechanisms and opportunities for cancer treatment (PID2022-139691OB-I00). PI: Raimundo Freire and Veronique Smits. Ministry of Science and Innovation (10/2023 – 09/2026, €400,000)
• Control of genome stability by KDM4 family demethylases and their connection to cancer (PIFIISC21/16). PI: Veronique Smits. Canary Islands Foundation for Health Research, FIISC (01/2022 – 12/2024, €21,750)

Publications 2023:

• Hernández‐Carralero E, Cabrera E, Rodríguez‐Torres G, Hernández‐Reyes Y, Singh AN, Santa‐María C, Fernández‐Justel JM, Janssens RC, Marteijn JA, Evert BO, Mailand N, Gómez M, Ramadan K, Smits VAJ, Freire R. ATXN3 controls DNA replication and transcription by regulating chromatin structure. Nucleic acids research. 2023;51(11):5396-413. DOI: 10.1093/nar/gkad212

Other representative publications from recent years:

• Warmerdam DO, Alonso-de Vega I, Wiegant WW, van den Broek B, Krawitowska-Rother MB, Freire R, van Attikum H, Medema RH, Smits VAJ. PHF6 promotes non-homologous end joining and G2 checkpoint recovery. EMBO Rep. 2020. 21: e48460. DOI: 10.15252/embr.201948460
• Alonso-de Vega I, Paz-Cabrera MC, Rother MB, Wiegant WW, Checa-Rodríguez C, Hernández-Fernaud JR, Huertas P, Freire R, van Attikum H, Smits VAJ. PHF2 regulates homology-directed DNA repair by controlling the resection of DNA double strand breaks. Nuclear Acids Res. 2020. 48: 4915-4927. DOI: 10.1093/nar/gkaa196
• Smits VAJ, Alonso-de Vega I, Warmerdam DO. Chromatin regulators and their impact on DNA repair and G2 checkpoint recovery. Cell Cycle. 2020. 19: 2083-2093. DOI: 10.1080/15384101.2020.1796037