Transcription-Replication Conflicts in Eukaryotes
RESEARCH FELLOW
Esther Ortega
Ramón y Cajal Fellow
Research Summary
Our group aims to understand the molecular mechanisms that maintain eukaryotic genome stability during DNA replication, using a combination of biochemical, biophysical, cellular and structural techniques.
Research Lines
Our group has been established in 2021 and aims to understand the molecular mechanisms that maintain eukaryotic genome stability during DNA replication, using a combination of biochemical, biophysical, cellular and structural techniques. DNA replication and RNA transcription are two essential processes required for accurate cell function and the propagation of genetic information. As both machineries need to access to the same DNA substrate, efficient coordination between these two processes is essential to maintain the integrity of the genome. However, these machineries can meet in space and time, causing transcription-replication conflicts (TRCs), which are a main cause of genomic instability. In eukaryotic organisms, TRCs interfere with the progression and stability of the replication forks and also trigger the accumulation of dangerous recombinant DNA structures (as R-loops) which slows down or stalls replication forks due to the physical impediments that prevents its advance. Stalled forks are a threat for DNA duplication and genome stability, causing neurodegeneration and cancer. Our group is focused on understanding the role of several factors important in the resolution of TRCs. We aim to elucidate how human Senataxin and PCNA_unloading complexes protects the integrity of the replication machinery and resolve R-loops structures formed during these TRCs.
The DNA replication machinery (replisome) is a multi-protein complex which must overcome diverse ‘obstacles’ as R-loops and RNA Polymerase to faithfully replicate DNA. This is done by recruiting other factors, as Senataxin or PCNA-unloading complex. Our group investigates the molecular mechanisms of the function of these proteins.
Publications
Group Members
Group Leader
Esther Ortega
Technician
Eduardo Muñoz
PhD candidate
José Manuel Aguilella
Funding
Our research is funded by national and international institutions as indicated below. For more details, please check the general Funding Section at the CNB website.
News
Real-space heterogeneous reconstruction, refinement, and disentanglement of CryoEM conformational states with HetSIREN
Nat Commun. 2025 Apr 22;16(1):3751. Herreros D, Mata CP, Noddings C, Irene D, Krieger J, Agard DA, Tsai MD, Sorzano COS, Carazo JM. Abstract Single-particle analysis by Cryo-electron microscopy (CryoEM) provides direct access to the conformations of...
Ceftazidime-avibactam use selects multidrug-resistance and prevents designing collateral sensitivity-based therapies against Pseudomonas aeruginosa
Nat Commun. 2025 Apr 9;16(1):3323. Hernando-Amado S, Gomis-Font MA, Valverde JR, Oliver A, Martínez JL Abstract Ceftazidime-avibactam is a β-lactam/β-lactamase inhibitor combination restricted for the treatment of multidrug-resistant infections of Pseudomonas...
El Centro Nacional de Biotecnología estrena nueva imagen para reflejar una etapa de renovación y evolución
El nuevo logotipo está compuesto por una espiral que representa una hélice de ADN vista desde arriba, inspirada en la emblemática “Fotografía 51” de Rosalind Franklin, clave para desentrañar su estructura La presentación de esta imagen coincide con el Día del ADN, una...