Academic Track

I obtained a MD degree (Medicine & Surgery) in 1984 from the University of Barcelona, a MS degree in Structural and Molecular Biology in 1985 from the Technology University of Catalonia, and a PhD degree in 1988 from the University of Barcelona with an awarded Doctoral Thesis on Chromosomal DNA Topology. In 1988, I moved to Harvard University to continue my research, three years as Postdoctoral Fellow and five years as Research Associate. In 1996, I returned to Spain as Staff Scientist of the Spanish Research Council (CSIC) to create the DNA Topology Lab at the Molecular Biology Institute of Barcelona (IBMB). Since then, I supervised eleven Doctoral Thesis. I was promoted to Full Professor in 2008 and ranked within the world’s top 2% most influential scientists in 2021.

I was chairman of the Molecular and Cellular Biology Department of the IBMB (2002-2006), Deputy Director of the IBMB (2006-2010) and Member of the CSIC Advisory Board of Biology and Biomedicine (2012-2023). Currently, I chair the Structural and Molecular Biology Department of the IBMB.

Scientific Vision

My objective within the realm of science is to produce groundbreaking contributions that advance the frontier of knowledge and inspire fellow researchers. To achieve this, I intentionally avoid working on trendy topics, where intense competition for high visibility and publication records often compromises scientific rigor and creativity. Instead, I focus on addressing fundamental questions that remain overlooked or unamenable with mainstream technologies. I enjoy developing innovative approaches and conducting original experiments aimed at producing genuinely novel and insightful discoveries.

Research Interest

Since my college years, I have been intrigued by how long DNA molecules fold and organize into compact structures known as chromosomes. This fascination has driven my research to explore the interplay between the structural elements, enzymes and motor activities that determine the topology of intracellular DNA. Despite the methodological limitations and the small number of experts in this field, I firmly believe that only after revealing the topology of intracellular DNA will we have a comprehensive understanding of the intricate nanomechanics that govern genome biology and its dysfunctions.

Research Lines

DNA HANDLERS

I exploit DNA topological methods to study the mechanism of Type-2 topoisomerases and SMC complexes. These two enzymatic complexes are nano-machines essential for folding and organizing DNA molecules into chromosomes. They are highly conserved in all life forms (from bacteria to eukaryotes).

DNA TANGLES

I perform high-resolution two-dimensional gel electrophoresis to analyze the broad-spectrum DNA supercoils, links and knots that occur in biological systems. These topological invariants capture the spatial trajectory of DNA and reveal its alterations produced by the structural and functional elements of chromatin.

TOPOLOMICS

I develop novel approaches to uncover the genome-wide topology of intracellular DNA (Topolome). I inspect how the structural elements of chromatin fold and constrain the DNA double helix alongside the chromosomes (Constrained Topolome); and how the motor activities that populate the genome pull, twist, and bend the DNA (Unconstrained Topolome).

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 -under review- (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