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
  • Mechanisms preventing irreversible replication fork arrest
  • Functions of histone deacetylases at replication forks

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. I developed 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 the ubiquitous accumulation of co-transcriptional R-loops impair replication fork progression and identified that as a major cause of transcription-associated genetic instability. 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 moved to UK in 2010 to work in the laboratory of Dr. John Diffley at Clare Hall Laboratories (belonging to CRUK until April 2015 and to The Francis Crick Institute since then), where I studied 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. Back to Spain in 2015, I continued my interest in the role of chromatin in recombination at forks. I also contributed to identify new genes involved in the prevention or resolution of R-loops in yeast and human cells and explored the causes of DNA-RNA hybrid accumulation in human cells deficient in the tumor suppressor gene BRCA2. Altogether my research lines include the study of causes and consequences of replication fork damage focusing on the role of chromatin, and in particular histone acetylation, in the repair of replication-induced damage, in transcription-replication conflicts and in the mechanisms preventing irreversible arrest 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

Research team:

  • Mecanismos de Inestabilidad Genómica mediada por ARN y Reparación. Ministerio de Ciencia, Innovación y Universidades. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2019-2022.
  • Transcripción y Replicación como Fuentes de Inestabilidad Genética. Ministerio de Economía y Competitividad. IP: Aguilera-López, Andrés (Universidad de Sevilla). 2016-2019.

Researcher: 

  • 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
  • ERC Advanced Grant: The Initiation of Eukaryotic DNA Replication: Mechanism, Regulation and Role in Genome Stability. EUKDNAREP European Research Council. 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*, Sessa G, Carreira A, Aguilera A (2021) A new interaction between BRCA2 and DDX5 promotes the repair of DNA breaks at transcribed chromatin Mol Cell Onc DOI: 10.1080/23723556.2021.1910474 * Corresponding author
  1. Sessa G*, Gómez-González B*, Silva S, Pérez-Calero C, Beaurepere R, Barroso S, Martineau S, Martin C, Ehlén A, Martínez JS, Lombard B, Loew D, Vagner V, Aguilera A, Carreira A (2021) BRCA2 promotes DNA-RNA hybrid resolution by DDX5 at DNA breaks to facilitate their repair. EMBO J 40(7):e106018. *Co-first author
  2. Gómez-González B*, Aguilera A. (2021) Origin matters: spontaneous DNA-RNA hybrids do not form in trans as a source of genome instability. Curr Genet. 67:93-97. *Co-corresponding author
  3. Lafuente-Barquero J, Garcia-Rubio ML, San Martin-Alonso M, Gómez-González B* and Aguilera A* (2020) Harmful DNA:RNA hybrids are formed in cis and in a Rad51-independent manner. eLife 9, e56674 *Co-corresponding author
  4. Gómez-González B and Aguilera A. (2020) Looping the (R) loop in DSB repair via RNA methylation Mol Cell 3, 361-362
  5. Ortega P, García-Pichardo D, San Martin-Alonso M, Rondón AG, Gómez-González B* and Aguilera A* (2020) Histone H3E73Q and H4E53A mutations cause recombinogenic DNA damage Microb Cell 7, 190-198. *Co-corresponding author
  6. Gómez-González B*, Barroso S, Herrera-Moyano E, and Aguilera A. (2020) Spontaneous DNA-RNA hybrids: differential impacts throughout the cell cycle. Cell Cycle, 19(5):525-531. * Corresponding author
  7. Gómez-González B*, Ortega P, and Aguilera A*. (2020) Histone deacetylases facilitate the accurate repair of broken forks Mol Cell Onc 7(2):1705731. * Co-corresponding author
  8. Ortega P, Gómez-González B* and Aguilera A* (2019) Rpd3L and Hda1 histone deacetylases facilitate repair of broken forks by promoting sister chromatid cohesion. Nat Comm 10, 5178. ** Co-corresponding author
  9. 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 R 20, e47250.
  10. Gómez-González B, Aguilera A (2019) Transcription-mediated replication hindrance: a major driver of genome instability. Genes Dev 33, 1008-1026.
  11. 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. Microb Cell 6, 1-64.
  12. Gómez-González 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.
  13. Aguilera A and Gómez-González B (2017) The need to regulate replication fork speed. Science 358, 722-723.
  14. 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.
  15. Bhatia V, Herrera-Moyano E, Aguilera A, Gómez-González B* (2017). The Role of Replication-Associated Repair Factors on R-Loops. Genes 8(7) pii: E171. * Co-corresponding author
  16. García-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.
  17. Aguilera A, Gómez-González B (2017). DNA-RNA hybrids: the risks of DNA breakage during transcription. NSMB 24(5), 439-443.
  18. 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 author
  19. Yekezare M, Gómez-González B and Diffley JF (2013) Controlling DNA replication origins in response to DNA damage – inhibit globally, activate J. Cell Sci. 126, 1297-306.
  20. Bermejo R, Capra T, Jossen R, Colosio A, Frattini C, Carotenuto W, Cocito A, Doksani Y, Klein H, Gómez-González 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.
  21. Dominguez-Sanchez MS, Barroso S, Gómez-González B, Luna R and Aguilera A (2011). Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX. PLoS Genet 7, e1002386.
  22. Garcia-Rubio M, Gómez-González B, 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. *Co-first author
  23. Gómez-González B, Ruiz JF and Aguilera A (2011). Genetic and Molecular Analysis of Mitotic Recombination in Saccharomyces Cerevisiae. Methods Mol Biol 745, 151-172.
  24. Mischo HE, Gómez-González 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.
  25. Ruiz JF, Gómez-González 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.
  26. Gómez-González 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.
  27. Gómez-González 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.
  28. Pardo B, Gómez-González 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.
  29. Ruiz JF, Gómez-González 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.
  30. Aguilera A and Gómez-González B (2008). Genome Instability: A Mechanistic View of Its Causes and Consequences. Nat Rev Genet 9, 204-217.
  31. Gonzalez-Aguilera C, Tous C, Gómez-González 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.
  32. Gómez-González 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.