Rodrigo Bermejo

Research interest

DNA replication is a fascinating process allowing organisms to grow and propagate by generating virtually identical copies of their genetic material. However, problems during replication can generate genomic instability linked to human disease. Our main interest is to understand the mechanisms that protect chromosome integrity during replication. For this we employ a multidisciplinary approach combining genetics, genomics and molecular biology.

DNA replication has a dark side for the cell as it is carried out in specialized structures (replication forks) that are intrinsically fragile and prone to engage in unscheduled recombination events. Replication fork progression can stall when DNA synthesis is inhibited or when forks interfere with other chromosome metabolic processes (e.g. gene transcription or DNA repair). In these situations stalled forks tend to collapse and generate DNA breaks. Aberrant repair of such collapsed forks, particularly in the context of defective cellular response to DNA damage, gives rise to mutations and chromosomal rearrangements, hallmarks of malignant transformation.

There are two main research projects in the laboratory. The first one focuses on elucidating the molecular mechanisms that protect the integrity of stalled replication forks to preserve their ability to carry out DNA synthesis. We are interested in the contribution of several nuclease activities to the resection of replication intermediates upon fork stalling. These activities influence fork stability and mediate transitions at replication forks that determine the formation of DNA breaks and chromosomal rearrangements. We are also studying how chromosome-organizing factors, such as the cohesin complex, contribute to maintain the architecture of fork DNA and replication machineries to protect replication integrity.

A second project focuses on understanding how cells avoid fork collapse upon interference with gene transcription. Fork collapse upon clashing with transcription has emerged as a major potential cause of DNA damage in precancerous cells. We are studying the role of factors involved in mRNA processing in handling the topology of transcribed chromatin. We aim at characterizing their ability to relieve torsional stress generated upon convergence of replication and transcription machineries and thus prevent the formation of aberrant structures that challenge fork progression and stability.

Publications

  • Arianna Colosio, Camilla Frattini, Grazia Pellicanò, Sara Villa-Hernández and Rodrigo Bermejo. [2016]. Nucleolytic processing of aberrant replication intermediates by an Exo1-Dna2-Sae2 axis counteracts fork collapse-driven chromosome instability. Nucleic Acids Research, Sep 16.

  • Gonzalez-Huici V., Szakal B., Urulangodi M., Psakhye I., Castellucci F., Menolfi D., Rajakumara E., Fumasoni M., Bermejo R., Jentsch S., Branzei D. [2014]. DNA bending facilitates the error-free DNA damage tolerance pathway and upholds genome integrity. EMBO J 33: 327-40.

  • Jossen R, Bermejo R. [2013]. The DNA damage checkpoint response to replication stress: A Game of Forks. Front Genet. 4: 26.

  • Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, Saponaro M, Brambati A, Cocito A, Foiani M, Liberi G. [2012]. Senataxin Associates with Replication Forks to Protect Fork Integrity across RNA-Polymerase-II-Transcribed Genes. Cell 151: 835-46.

  • Bermejo R, Kumar A, Foiani M. [2012]. Preserving the genome by regulating chromatin association with the nuclear envelope. Trends Cell Biol. 2012 Sep;22(9):465-73.

  • Bock LJ, Pagliuca C, Kobayashi N, Grove RA, Oku Y, Shrestha K, Alfieri C, Golfieri C, Oldani A, Dal Maschio M, Bermejo R, Hazbun TR, Tanaka TU, De Wulf P. [2012]. Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore. Nat Cell Biol. 2012 May 6;14(6):614-24.

  • Bermejo R, Lai MS, Foiani M. [2012]. Preventing replication stress to maintain genome stability: resolving conflicts between replication and transcription. Mol Cell. 2012 Mar 30;45(6):710-8.

  • Ray Chaudhuri A, Hashimoto Y, Herrador R, Neelsen KJ, Fachinetti D, Bermejo R, Cocito A, Costanzo V, Lopes M. [2012]. Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Nat Struct Mol Biol. 2012 Mar 4;19(4):417-23.

Active Grants

  • BFU2014-52529-R (MINECO) (2015-2017)

Group members

  • Rodrigo Bermejo (Group leader)
  • Grazia Pellicanò (PhD student)
  • Martin Andrš (PhD student)