Centro Andaluz de Biología Molecular y Medicina Regenerativa
Belen Gomez Gonzalez

e-mail: belen.gomez@cabimer.es

Main Research lines

  • Transcription-associated genetic instability and R-loops
  • The role of S-phase checkpoints in the stabilisation of replication forks
  • Functions of histone deacetylases at replication forks
  • Role of BRCA2 and related factors in the resolution of R-loops and prevention of cancer-associated genome instability

My research interests have focused on transcription and replication as main sources of genetic instability. During my PhD, I worked with Prof. Andrés Aguilera on transcription, and R-loops in particular, as a source of genetic instability. My PhD, funded by an FPU fellowship, was awarded in 2009 with ‘Sobresaliente Cum Laude’, European Mention, and later on awarded with the ‘Premio Extraordinario de Doctorado’. I development powerful genetic tools for the identification of R-loops in vivo by the heterologous over-expression of human AID in yeast mutants of the THO complex, involved in mRNP biogenesis. I also contributed to show that co-transcriptional R-loops impair replication fork progression and identified that as the main cause of transcription-associated genetic instability. I further showed that the phenotypes of THO mutants could be observed genome-wide. In agreement with R-loops being a frequent source of DNA damage, I showed that to survive replication stress, THO mutants require a functional S-phase checkpoint, known to be essential for the maintenance of replication fork stability.

I then decided to deepen my understanding of the replication process with a leading scientist in the field, Dr. John Diffley. For this purpose, I moved to UK in 2010 and worked at Clare Hall Laboratories (belonging to CRUK until April 2015 and to The Francis Crick Institute since then), where I was funded by a long-term EMBO Fellowship and by CRUK to work on the role of S-phase checkpoints in replication fork stabilization. Combining genome-wide sequencing with the power of classical genetics, I defined an unexpected link between histone deacetylation and fork stability. Further mechanistic insights allowed us to uncover the role of certain factors in irreversible fork arrest both in yeast and human cells.

In 2015, I was awarded a grant from the Spanish Association Against Cancer (AECC) and I re-joined Andrés Aguilera´s laboratory in CABIMER to work on the consequences of R-loops and transcription in general on replication forks. Since then, I am working on the mechanisms that might explain R-loop accumulation in human cells, in particular in BRCA2 deficient cells and its connection not only with the replication fork but also with other BRCA2-related functions, such as homologous recombination and mitosis. In parallel, I am working in the identification of new genes involved in the prevention or resolution of R-loops. During this time, I have supervised two Erasmus projects, and I am supervising two PhD projects, one focusing on the role of histone deacetylases in the repair of replication-born DNA breaks and the other one investigating the use of new methodologies to map R-loops genome-wide and screening for histone factors that can be involved in the prevention of R-loop accumulation.

ORCID: 0000-0003-1655-8407
ResearcherID: B-2365-2014
Scopus: 16678982400 

Principal Investigator:

  • Role of BRCA2 and related factors in the resolution of R-loops and prevention of cancer-associated genome instability. Ayuda a Investigadores en Oncología. Fundación científica de la AECC. 2015-2020

Investigator: 

  • Transcripción y Replicación como Fuentes de Inestabilidad Genética. Ministerio De Economía Y Competitividad. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2016-2019.
  • Inestabilidad Genómica Asociada a Transcripción e Híbridos DNA-RNA. Ministerio De Economía Y Competitividad. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2014-2016.
  • Deciphering the role of S-phase checkpoints in the stabilisation of replication forks. CRUK. IP: Diffley, JFX (Clare Hall laboratories) 2010-2015
  • DNA replication in Eukaryotes. EUKDNAREP 249883201 European Research Council-ERC Advanced. IP: Diffley, JFX (Clare Hall laboratories) 2010-2014
  • Inestabilidad Genómica. Plan Estatal 2013-2016 Redes de Excelencia. Ministerio de Economia y Competitividad. IP: Aguilera-López, Andrés (Universidad de Sevilla) BFU2014-51672-REDC 2013-2016.
  • Inestabilidad Genómica Asociada a Transcripción e Híbridos DNA-RNA. Plan estatal 2013-2016 Excelencia. Ministerio de Economia y Competitividad. IP: Aguilera-López, Andres (Universidad de Sevilla) BFU2013-42918-P 2013-2016.
  • Bases genéticas y moleculares del origen de la inestabilidad genómica en eucariotas. Junta de Andalucía. Proyecto de Excelencia CVI-4567. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2010-2013.
  • Inestabilidad Genómica, Grupo Bio-102. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2011
  • Genómica Funcional de la interconexión transcripción-transporte de ARN. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2008-2011
  • Inestabilidad Genómica CSD2007-00015. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2007-2013
  • Bases genéticas y moleculares de la instabilidad genómica en eucariotas. P09-CVI-4567 IP: Aguilera-López, Andrés (Universidad de Sevilla). 2010-2013
  • Inestabilidad Genómica. Grupo BIO-102 IP: Aguilera-López, Andrés (Universidad de Sevilla). 2009-2011
  • Inestabilidad Genómica. Grupo BIO-102 IP: Aguilera-López, Andrés (Universidad de Sevilla). 2009-2010
  • Inestabilidad Genómica. Grupo BIO-102 IP: Aguilera-López, Andrés (Universidad de Sevilla). 2007-2010
  • Vigilancia del ARN nuclear en la expresión génica BFU2007-28647-E IP: Aguilera-López, Andrés (Universidad de Sevilla). 2007-2010
  • Bases genéticas y moleculares de la instabilidad genómica y su relación con la biogénesis de los mRNPs en eucariotas. BFU2006-05260 IP: Aguilera-López, Andrés (Universidad de Sevilla). 2006-2011

Articles:

  1. Gomez-Gonzalez, B., Patel, H., Early, A., Diffley, JFX. (2019) Rpd3L contributes to the DNA damage sensitivity of Saccharomyces cerevisiae checkpoint mutants Genetics. 211:503-513.
  2. Klein HL, Bačinskaja G, Che J, Cheblal A, Elango R, Epshtein A, Fitzgerald DM, Gomez-Gonzalez B, et al. (2019) Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways. Microb Cell. 6:1-64.
  3. Aguilera A, Gomez-Gonzalez B, (2017) The need to regulate replication fork speed Science 358, 722-723.
  4. Lafuente-Barquero J, Luke-Glaser S, Graf M, Silva S, Gomez-Gonzalez B, Lockhart A, Lisby M, Aguilera A and Luke B The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage PLoS Genet. 13:e1007136.
  5. Bhatia V, Herrera-Moyano E, Aguilera A, Gomez-Gonzalez B* (2017). The Role of Replication-Associated Repair Factors on R-Loops. Genes (Basel). 8(7). pii: E171.* Corresponding author
  6. García-Pichardo D, Cañas JC, García-Rubio ML, Gomez-Gonzalez B, Rondón AG, Aguilera A (2017). Histone Mutants Separate R Loop Formation from Genome Instability Induction. Mol Cell. 66(5):597-609.e5.
  7. Aguilera A, Gomez-Gonzalez B (2017). DNA-RNA hybrids: the risks of DNA breakage during transcription. Nat Struct Mol Biol. 24(5):439-443.
  8. Muñoz-Galván S, García-Rubio M, Ortega P, Ruiz JF, Jimeno S, Pardo B, Gomez-Gonzalez B*, Aguilera A*. (2017) A new role for Rrm3 in repair of replication-born DNA breakage by sister chromatid recombination. PLoS Genet. 2017 May 5;13(5):e1006781. * Co-corresponding authors
  9. Yekezare M, Gomez-Gonzalez B and Diffley JF (2013) Controlling DNA replication origins in response to DNA damage – inhibit globally, activate J. Cell Sci. 126, 1297-306.
  10. Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W, Cocito A, Doksani Y, Klein H, Gomez-Gonzalez B, Aguilera A, Katou Y, Shirahige K and Foiani M (2011). The Replication Checkpoint Protects Fork Stability by Releasing Transcribed Genes from Nuclear Pores. Cell 146, 233-246.
  11. Dominguez-Sanchez MS, Barroso S, Gomez-Gonzalez B, Luna R and Aguilera A (2011). Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX. PLoS Genet 7, e1002386.
  12. Gomez-Gonzalez B, Garcia-Rubio M, Bermejo R, Gaillard H, Shirahige K, Marin A, Foiani M and Aguilera A (2011). Genome-Wide Function of THO/TREX in Active Genes Prevents R-Loop-Dependent Replication Obstacles. EMBO J 30, 3106-3119.
  13. Gomez-Gonzalez B, Ruiz JF and Aguilera A (2011). Genetic and Molecular Analysis of Mitotic Recombination in Saccharomyces Cerevisiae. Methods Mol Biol 745, 151-172.
  14. Mischo HE, Gomez-Gonzalez B, Grzechnik P, Rondon AG, Wei W, Steinmetz L, Aguilera A and Proudfoot NJ (2011). Yeast Sen1 Helicase Protects the Genome from Transcription-Associated Instability. Mol Cell 41, 21-32.
  15. Ruiz JF, Gomez-Gonzalez B and Aguilera A (2011). AID Induces Double-Strand Breaks at Immunoglobulin Switch Regions and C-Myc Causing Chromosomal Translocations in Yeast THO Mutants. PLoS Genet 7, e1002009.
  16. Gomez-Gonzalez B and Aguilera A (2009). R-Loops Do Not Accumulate in Transcription-Defective Hpr1-101 Mutants: Implications for the Functional Role of THO/TREX. Nucleic Acids Res 37, 4315-4321.
  17. Gomez-Gonzalez B, Felipe-Abrio I and Aguilera A(2009). The S-Phase Checkpoint Is Required to Respond to R-Loops Accumulated in THO Mutants. Mol Cell Biol 29, 5203-5213.
  18. Pardo B, Gomez-Gonzalez B and Aguilera A (2009). DNA Repair in Mammalian Cells: DNA Double-Strand Break Repair: How to Fix a Broken Relationship. Cell Mol Life Sci 66, 1039-1056.
  19. Ruiz JF, Gomez-Gonzalez B and Aguilera A (2009). Chromosomal Translocations Caused by Either Pol32-Dependent or Pol32-Independent Triparental Break-Induced Replication. Mol Cell Biol 29, 5441-5454.
  20. Aguilera A and Gomez-Gonzalez B (2008). Genome Instability: A Mechanistic View of Its Causes and Consequences. Nat Rev Genet 9, 204-217.
  21. Gonzalez-Aguilera C, Tous C, Gomez-Gonzalez B, Huertas P, Luna R and Aguilera A (2008). The Thp1-Sac3-Sus1-Cdc31 Complex Works in Transcription Elongation-mRNA Export Preventing RNA-Mediated Genome Instability. Mol Biol Cell 19, 4310-4318.
  22. Gomez-Gonzalez B and Aguilera A (2007). Activation-Induced Cytidine Deaminase Action Is Strongly Stimulated by Mutations of the THO Complex. Proc Natl Acad Sci USA 104, 8409-8414.