Academic Track

1984  MD degree (Medicine & Surgery). University of Barcelona. Distinction with honours.
1985  MS degree in Structural and Molecular Biology. Technology University of Catalonia,
1988   PhD degree at University of Barcelona. First Prize Doctoral Thesis.
1988-1991 Postdoctoral Fellow. Dep of Biochemistry and Molecular Biology. Harvard University.
1992-1996. Research Associate. Dep of Biochemistry and Molecular Biology. Harvard University.
1996  Staff Scientist. Spanish Research Council (CSIC).
1997  Leader of the DNA Topology Lab. Molecular Biology Institute of Barcelona (IBMB).
2008  Full Professor of Biology and Biomedicine (CSIC).

Chair of the Molecular and Cellular Biology Department of the IBMB (2002-2006),
Deputy Director of the IBMB (2006-2010).
Member of the CSIC Advisory Board of Biology and Biomedicine (2012-2023).
Chair of the Structural and Molecular Biology Department of the IBMB (2023-present).
Director of eleven Doctoral Thesis at the DNA Topology Lab (1997-present)
Ranked within the world’s top 2% most influential scientists (2021).

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Scientific Vision

My goal in science is to make groundbreaking contributions that push the boundaries of knowledge and inspire future research. I consciously avoid pursuing trendy topics where competition for visibility and publication often compromises scientific rigor and creativity. Instead, I dedicate my efforts to addressing fundamental questions that are frequently overlooked or considered intractable with current technologies. By conceptualizing novel ideas and exploring them through innovative approaches, I aim to achieve authentic discoveries that leave a lasting impact.

Research Interest

Since my college years, I have been fascinated by how long DNA molecules fold into chromosomes to ensure accurate replication and the proper execution of gene expression programs. This curiosity led me to focus my research on the interplay between structural elements and motor activities that regulate DNA topology within cells. Despite the methodological challenges and the relatively small number of specialists in this field, I am convinced that uncovering how the DNA double helix is pulled, twisted, and bent at each chromosomal locus is key to understanding the intricate nanomechanics that govern genome biology and its dysfunctions.

Research Lines

DNA HANDLERS

I employ DNA topology-based methods to investigate the mechanisms of Type-2 topoisomerases and SMC complexes. These enzymatic ensembles act as highly conserved nanomachines across all forms of life, from bacteria to eukaryotes, playing a crucial role in folding and organizing DNA into chromosomes.

DNA TANGLES

I develop high-resolution two-dimensional gel electrophoresis techniques to analyze a broad spectrum of DNA supercoils, links, and knots found in biological systems. These topological invariants provide insights into the spatial trajectory of DNA and uncover its deformations caused by the structural and functional elements of chromatin.

TOPOLOMICS

I develop innovative approaches to map the genome-wide topology of intracellular DNA, referred to as the "Topolome." This research has two scopes: the Constrained Topolome, which examines how chromatin's structural elements deform the folded DNA double helix along chromosomes, and the Unconstrained Topolome, which investigates how motor activities transiently pull, twist, and bend the DNA.

Main Accomplishments

• Uncovering the two-gate mechanism of type-II topoisomerases (Cell 1992, PNAS 1994, Cell 1994, TiBS 1995, PNAS 1996, JBC 2004, NAR 2009), currently depicted in the text-books.


• Clarifying the DNA transport preferences of eukaryotic topoisomerase II and deciphering its mechanism to simplify DNA topology to below equilibrium values (JBC 1993, GenCells 1996, JMB 2001, GenCells 2002, JMB 2004, NAR 2014).


• Pioneering analyses of the interplay of topoisomerase activities with chromatin structure (EMBO 1989, JBC 2001, JBC 2002, EMBO 2006, EMBO 2010, NAR 2012, NAR 2013, EMBO 2014). These studies uncovered: (i) that topoisomerase II is the main relaxase of nucleosomal DNA; and (ii) that unbalanced relaxation of (+) and (-) supercoils by topoisomerase II produces a prevalence of (-) supercoiled DNA in eukaryotic chromatin.


• Measuring of the DNA deformation produced by CEN proteins to describe the molecular architecture and distinctive right-handed DNA topology of point centromeres (Cell Rep 2015).


• Measuring of the average topology of nucleosomal DNA, which revealed a DNA linking number  difference (∆Lk) of about -1.26 (Nature com 2018). This ∆Lk value solved the "linking number paradox of nucleosomal DNA", which puzzled scientists over decades.


• Pioneering analyses of DNA knots as a footprint of the 3D path of and biophysical properties of DNA and chromatin. These analyses demonstrated the chiral folding of DNA in viruses (NAR 2001, PNAS 2002, PNAS 2005) and exposed the packaging dynamics of DNA in eukaryotic chromatin (NAR 2018, NAR 2019b).


• Uncovering a new role of the SMC complex -condensin- in minimizing intracellular DNA entanglements (EMBO 2021, BioEssays 2022)


• Uncovering a "DNA pinch and merge mechanism" of condensin to made DNA translocation steps during the process of DNA loop extrusion (EMBO 2023).


• Topolomics: Performing the first analysis of psoralen:DNA photo-binding to map DNA supercoiling in vivo (NAR 2010, EMBO 2010), a method now broadly used.


• Topolomics: Development of "Topo-seq", a novel procedure to inspect the topology of large libraries of DNA circles in a single gel electrophoresis. Topo-seq revealed that the topology of nucleosomal DNA is imprinted by the native genomic loci (Nature com, 2024).

Selected Publications

• Nucleosomal DNA has topological memory. Segura, Díaz-Ingelmo, Martínez-García, Ayats-Fraile, Nikolaou and Roca* bioRxiv DOI:10.1101/2023.05.21.541612.   Nature Com (2024)


• Condensin pinches a short negatively supercoiled DNA loop during each round of ATP usage. Martínez-García, Dyson, Segura, Gutierrez-Escribano, Aragón, and Roca* EMBO J  -e111913 (2023)


• Condensin minimizes topoisomerase II-mediated entanglements of DNA in vivo. Dyson, Segura, Martínez-García, Valdés, and Roca*. EMBO J - e105393 (2021)


• Transcriptional supercoiling boosts topoisomerase II-mediated knotting of intracellular DNA. Valdés, Coronel, Martínez-García, Segura, Dyson, Díaz-Ingelmo, Micheletti, and Roca* Nucleic Acids Res. 47:6946-6955 (2019)


• Quantitative disclosure of DNA knot chirality by high-resolution 2D-gel electrophoresis Valdés, Martínez-García, Segura, Dyson, Díaz-Ingelmo and Roca* Nucleic Acids Res. 47:e29 (2019)


• Intracellular nucleosomes constrain a DNA linking number difference of -1.26 that reconciles the Lk paradox. Segura, Joshi, Díaz-Ingelmo, Valdés, Dyson, Martínez-García and Roca* Nature Com 28:3989 (2018)


• DNA knots occur in intracellular chromatin. Valdes, Segura, Dyson,Martinez-Garcia and Roca* Nucleic Acids Res 46, 650-660 (2018)


• DNA Topology and Global Architecture of Point Centromeres. Diaz-Ingelmo, Martinez-Garcia, Segura, Valdes and Roca* Cell Reports 13, 667-677 (2015)


• Topoisomerase II minimizes DNA entanglements by proofreading DNA topology after DNA strand passage. Martinez-Garcia, Fernandez, Diaz-Ingelmo, Rodriguez-Campos, Manichanh and Roca* Nucleic Acids Res 42, 1821-1830 (2014)


• Chromatin regulates DNA torsional energy via topoisomerase II-mediated relaxation of positive supercoils. Fernandez, Diaz-Ingelmo, Martinez-Garcia and Roca* EMBO J 33, 1492-1501 (2014)


• Topoisomerase II regulates yeast genes with singular chromatin architectures. Nikolaou, Bermudez, Manichanh, Garcia-Martinez, Guigo, Perez-Ortin and Roca* Nucleic Acids Res. 41, 9243-9256 (2013)


• Topoisomerase II is required for the production of long Pol II gene transcripts in yeast. Joshi, Piña and Roca* Nucleic Acids Res 40, 7907-7915 (2012)


• Positional dependence of transcriptional inhibition by DNA torsional stress in yeast chromosomes.  Joshi, Pina and Roca* EMBO J 29, 740-748 (2010)


• Topoisomerase II, not topoisomerase I, is the proficient relaxase of nucleosomal DNA.  Salceda, Fernandez and Roca* EMBO J 25, 2575-2583 (2006)


• DNA knots reveal a chiral organization of DNA in phage capsids. Arsuaga, Vazquez, McGuirk, Trigueros, Sumners and Roca* PNAS USA 102, 9165-9169 (2005)


• Knotting probability of DNA molecules confined in restricted volumes: DNA knotting in phage capsids.  Arsuaga, Vazquez, Trigueros, Sumners and Roca* PNAS USA 99, 5373-5377 (2002)


• DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism.  Roca, Berger, Harrison and Wang. PNAS USA 93, 4057-4062 (1996)


• DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism.  Roca and Wang. Cell 77, 609-616 (1994).


• Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp. Roca, Ishida, Berger, Andoh, and Wang. PNAS USA  91, 1781-1785 (1994)


• The capture of a DNA double helix by an ATP-dependent protein clamp: a key step in DNA transport by type II DNA topoisomerases. Roca and Wang.  Cell 71, 833-840 (1992)


• DNA topoisomerase II activity in nonreplicating, transcriptionally inactive, chicken late spermatids. Roca and Mezquita. EMBO J 8, 1855-1860 (1989).

Full  list of publications