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. The combination of whole-genome sequencing technics with classic genetics allowed me to describe that the Rpd3L histone deacetylase complex is responsible for the DNA damage sensitivity of checkpoint mutants. I then searched for the essential factors involved in fork destabilization in yeast and human cells, uncovering an unexpected link with recombination. Thanks to a grant from the AECC, I was back to Spain in 2015, where I continued my interest in the role of chromatin in recombination at forks. We recently reported that Rpd3L and Hda1 histone deacetylases are essential for the repair of broken forks, and we are currently pursuing this work by the use of histone deacetylases inhibitors in human cell cultures.

I have also contributed to identify new genes involved in the prevention or resolution of R-loops in yeast and human cells. In parallel, I work on the causes and consequences of R-loop accumulation on human cells deficient in the tumor suppressor gene BRCA2 with the aim of understanding the molecular basis of tumorigenesis. Altogether my research lines focus on the role of chromatin, and in particular histone acetylation, in the repair of replication-induced damage and in transcription-replication conflicts in yeast and human cells.

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: 

  • ERC Advanced Grant: R-loops as a major modulator of transcription-associated recombination and chromatin dynamics TARLOOP European Research Council. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2015-2020.
  • 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. Gómez-González B*, Barroso S, Herrera-Moyano E, and Aguilera A. Spontaneous DNA-RNA hybrids: differential impacts throughout the cell cycle. Cell Cycle, in press *Corresponding author
  2. Gomez-Gonzalez B*, Ortega P, and Aguilera A. Histone deacetylases support the accurate repair of broken forks. Cell. Oncology in press *Corresponding author
  3. Ortega P, Gomez-Gonzalez, B* and Aguilera A* Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion. Nature Commun. 10, 5178. * Co-corresponding authors
  4. Barroso S, Herrera-Moyano E, García-Rubio ML, Gómez-González B, Aguilera A (2019) The DNA Damage Response acts as a safeguard against harmful DNA-RNA hybrids of different origins. EMBO Reports, 20, e47250.
  5. Gomez-Gonzalez B, Aguilera A (2019) Transcription-mediated replication hindrance: a major driver of genome instability. Genes Dev. 33, 1008-1026.
  6. Klein H., Bacinskaja G, Che J, Cheblal A, Elango R, Ephstein A, Fitzgerland D, Gómez-González B et al, (2019) Guidelines for DNA recombination and repair studies: Cellular assays of DNA repair pathways. Microbial Cell. 6, 1-64.
  7. Gomez-Gonzalez B, Patel H, Early A and Diffley JFX (2019) Rpd3L contributes to the DNA damage sensitivity of Saccharomyces cerevisiae checkpoint mutants. Genetics, 211, 503-513.
  8. Aguilera A, Gómez-González B, (2017) The need to regulate replication fork speed. Science 358, 722-723.
  9. Lafuente-Barquero J, Luke-Glaser S, Graf M, Silva S, Gómez-González B, Lockhart A, Lisby M, Aguilera A and Luke B (2017) The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage PLoS Genet. 13:e1007136.
  10. Bhatia V, Herrera-Moyano E, Aguilera A, Gómez-González B* (2017). The Role of Replication-Associated Repair Factors on R-Loops. Genes (Basel). 8(7). pii: E171. * Corresponding author
  11. Garcia-Pichardo D, Cañas JC, Garcia-Rubio ML, Gómez-González B, Rondón AG, Aguilera A (2017). Histone Mutants Separate R Loop Formation from Genome Instability Induction. Mol Cell. 66(5), 597-609.e5.
  12. Aguilera A, Gómez-González B (2017). DNA-RNA hybrids: the risks of DNA breakage during transcription. Nat Struct Mol Biol. 24(5), 439-443.
  13. Muñoz-Galván S, García-Rubio M, Ortega P, Ruiz JF, Jimeno S, Pardo B, Gómez-González 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
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Aguilera A and Gomez-Gonzalez B (2008). Genome Instability: A Mechanistic View of Its Causes and Consequences. Nat Rev Genet 9, 204-217.
  26. 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.
  27. 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.