Biography

The main objective of my scientific career has been to understand the mechanisms that maintain genome integrity. My work has been focused in two major research lines: 1) Mechanisms of Homologous Recombination (HR) and 2) Roles of chromatin in genome integrity. The major achievements of my work during my PhD (University of Seville 1991-1996) and Postdoc (Marburg University 1996-2000; University of Seville 2000-2005) were the finding of transcription as a potential source of HR-mediated genetic instability (EMBO J 1997), in particular as a consequence of transcription/replication collisions (EMBO J 2005), the regulatory role of nucleosome positioning in transcription (JBC 2002), and the importance of nucleosome assembly in preventing unscheduled HR (EMBO R 2004; MCB 2005). The major contributions of my research as Principal investigator (CABIMER-CSIC 2006-) can be summarized in the following points:

1. Cell-cycle regulation of HR during DNA damage tolerance (DDT), which in contrast to double-strand break (DSB) repair is coupled to replication and regulated in a spatiotemporal manner (EMBO J. 2013). This led to the hypothesis that replicative and repair functions need to be separated to prevent the recombinogenic processing of damaged replication forks (BioEssays 2014). This study generated tools to follow the recombinational repair of DNA lesions during DDT (Method Mol Biol 2021).

2. The description for the first time of non-recombinogenic functions for the core HR proteins Rad51 and Rad52 in translesion synthesis (TLS) (EMBO R 2021), pointing to the hypothesis that these factors operate as a molecular switch to choose the DDT mechanism (reviewed in Genes 2021).

3. The description of non-canonical roles for the MCM helicase in genome integrity through physical and dynamic interactions with Rad51 and Rad52 to facilitate fork assistance through non-recombinogenic functions (Cell R 2021). This work has allowed us to propose the existence of a specialized compartment to assist stressed replication forks (reviewed in FEBS J 2023). Second, it interacts with the ribonucleotide reductase complex to regulate the dynamic of DNA repair centers (PloS Genetics 2024).

4. The critical role of replication-coupled chromatin assembly for HR during DDT (Cell R 2023), replication fork stability (EMBO R 2009; PLoS Genetics 2011), chromosome segregation and cohesin distribution (NAR 2014; Epigenetics and Chromatin 2019) and transcription elongation and splicing (PNAS 2015). These studies also revealed the importance of controlling the levels of histones to protect telomeres by HR during senescence (PLoS Genetics 2018; 2019) and the existence of mechanisms to restore defects in chromatin assembly (Scientific Rep 2023).

5. The role of the chromatin remodeller SWR in the generation of HR-mediated genetic instability and transcriptional defects in the absence of its substrate the histone variant H2A.Z (PLoS One 2009; cited in the seminal text book “Epigenetics”, Edt. By David Allis), revealing the pathogenic effects of unscheduled chromatin processing.

6. The mechanisms by which cells respond to broken replication forks (PLoS Genetics 2025).

These studies, funded by national and regional grants, and published in internationally prestigious journals, have allowed to build a research group with a reputed national and international experience in the field of genetic instability, as exemplified by invited reviews and seminars and successful collaborations with national and international researchers (Dr. Reyes, Seville; Dr. San Segundo, Salamanca; Dr. Ulrich, Germany; Dr. Luke, Germany; Dr. Heyer, USA, Dr. Vertegaal, Paises Bajos...).

Currently, I am Director of the Genome Biology Department in CABIMER from 2025 and Manager of the Molecular and Cellular Biology subarea (BIO area) of the Spanish Research Agency (AEI) from 2023. I have participated as member of different committees for the evaluation of national and international grants (ANEP; I-LINC, CSIC, CDA, Human Frontier Science Program; PICT, Argentina; ANR, France; Wellcome Trust, England; US-Israel BS,...), researchers (CSIC, Ramón y Cajal, Juan de la Cierva) and national and international thesis (30), and I have worked as reviewer for prestigious journals (Science, Science Advances, NCOMMS, EMBO J, …). In addition, I have been in charge of the Model Organism Unit in CABIMER for 15 years, coordinator of the national network “Chromosome dynamics and stability” (2016-2019), formed by 13 prestigious investigators, and coordinator of the group “Gene expression and genome dynamics” from SEBBM (2013-2016). Finally, I have participated in different Master programs from Seville and Salamanca Universities and I have been invited to national and international conferences.

Contributions to young researchers. I have directed 8 thesis (plus 2 in progress), 7 Master and 2 TFG, and trained several students in the frame of different programs (JAE-Intro, Garantía Juvenil,…). PhDs from my group are now working either in the Academy or Pharmaceutic industry.

Contributions to society. I have focused my work to basic research, which is in itself a major objective in science with unpredictable benefits for human being and society. I have collaborated with CABIMER in disseminating the importance of research through seminars to school students.