Detalle de: Transcription-Replication Conflicts in Eukaryotes

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.