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

Information

In my research career, I have focused on transcription and replication as main sources of genetic instability.
During the PhD, I worked 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 that the ubiquitous accumulation of co-transcriptional R-loops impairs replication fork progression placing it as a major cause of transcription-associated genetic instability. In agreement with R-loops being a frequent source of DNA damage, I ed 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 Clare Hall Laboratories (UK) in 2010 to get further insight 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.
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.
Since 2020, I am professor at the University of Seville and study the causes and consequences of replication fork damage, including in transcription-replication conflicts, as well as the mechanisms of fork stabilization and repair, focusing on the role of histone acetylation.

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

Projects

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
  • Replication fork stability and arrest in eukaryotic cells (US-1380058). Proyectos I+D+i FEDER Andalucía 2014-2020 – Emergente

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

Publications

Articles:

  1. Gómez-González B, Ortega P, and Aguilera A (2021) Analysis of repair of replication-born double-strand breaks by sister chromatid recombination in yeast Methods in Enzymology 661, 121-138
  2. Chacin E, Bansal P, Reusswig KU, Diaz-Santin LM, Ortega P, Vizjak P, Gómez-González B, Müller-Planitz F, Aguilera A, Pfander B, Cheung ACM, Kurat CF (2021) A CDK-regulated chromatin segregase promoting chromosome replication. Nat Commun 12(1):5224.
  3. Ortega P, Gómez-González B*, and Aguilera A (2021) Heterogeneity of DNA damage incidence and repair in different chromatin contexts DNA Repair 107, 103210. * Corresponding author
  4. Ortega P, Mérida-Cerro JA, Rondón AG, Gómez-González B* and Aguilera A* (2021) DNA-RNA hybrids at DSBs interfere with repair by homologous recombination. eLife 10, 10:e69881. * Co-corresponding author
  5. 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
  6. 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
  7. 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
  8. 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
  9. Gómez-González B and Aguilera A. (2020) Looping the (R) loop in DSB repair via RNA methylation Mol Cell 3, 361-362
  10. 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
  11. 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
  12. 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
  13. 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 Commun 10, 5178. ** Co-corresponding author
  14. 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.
  15. Gómez-González B, Aguilera A (2019) Transcription-mediated replication hindrance: a major driver of genome instability. Genes Dev 33, 1008-1026.
  16. 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.
  17. 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.
  18. Aguilera A and Gómez-González B (2017) The need to regulate replication fork speed. Science 358, 722-723.
  19. 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.
  20. 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
  21. 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.
  22. Aguilera A, Gómez-González B (2017). DNA-RNA hybrids: the risks of DNA breakage during transcription. NSMB 24(5), 439-443.
  23. 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
  24. Yekezare M*, Gómez-González B* and Diffley JF (2013) Controlling DNA replication origins in response to DNA damage – inhibit globally, activate locally. J. Cell Sci. 126, 1297-306. * Co-first author
  25. 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.
  26. 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.
  27. Gómez-González 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. *Co-first author
  28. Gómez-González B, Ruiz JF and Aguilera A (2011). Genetic and Molecular Analysis of Mitotic Recombination in Saccharomyces Cerevisiae. Methods in Mol Biol 745, 151-172.
  29. 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.
  30. 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.
  31. 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.
  32. 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.
  33. 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.
  34. 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.
  35. Aguilera A and Gómez-González B (2008). Genome Instability: A Mechanistic View of Its Causes and Consequences. Nat Rev Genet 9, 204-217.
  36. 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.
  37. 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.