Centro Andaluz de Biología Molecular y Medicina Regenerativa
José Francisco Ruiz Pérez
Email: jose.ruiz@cabimer.es

 

Main Research Lines:

  1. Uncovering new roles of human PolX DNA polymerases.
  1. Structure-function analysis of human DNA polymerases specialized in DNA repair and DNA damage tolerance
  1. Regulation of DNA damage response proteins by post-translational modifications.
  1. Molecular basis of DSB repair and genetic instability.

My research career has focused on understanding how cells maintain the stability of their genome throughout their life, investigating the molecular basis of DNA replication, damage and repair processes that take place in eukaryotic cells. During my PhD at Centro de Biología Molecular “Severo Ochoa” (Universidad Autónoma de Madrid/CSIC) I was trained in Biochemistry and Molecular Biology, and I contributed to the identification and initial characterization of two novel human DNA polymerases of the PolX family, Pol lamba and Pol mu. This work generated many original research articles, having special relevance those in which these proteins were initially described (Dominguez and Ruiz et al. EMBO J. 2000; García-Díaz et al. J. Mol. Biol. 2001) and those uncovering biochemical features of human Pol mu and its functional roles in mammalian cells through diverse structure/function and in vivo analyses (Ruiz et al. Nucleic Acids Res 2003 and 2004).

During my postdoctoral stage, I was trained in Genetics in the laboratory of Prof. A. Aguilera, at the Department of Genetics of the Universidad de Sevilla, where my work was primarily focused on deciphering the molecular basis of genetic instability in eukaryotic cells, paying particular attention to mechanisms that generate and repair DNA double strand breaks (DSBs). This research allowed us both to identify new sources of DNA DSBs (Ruiz et al. PLoS Genetics 2011) and to characterize novel pathways for the maintenance of genome integrity after such DNA damage (Ruiz et al. Mol. Cell. Biol. 2009). Afterwards, I combined my previous expertise and skills to identify the role and regulation of PolX polymerases during the non-homologous end joining-mediated repair of DSBs that result in the formation of chromosomal translocations, a particular type of genomic rearrangements with a strong oncogenic potential. This original research was my first work as a senior PI (Ruiz et al. PLoS Genetics 2013), and was possible thanks to the JAE-Doc fellowship that I gained from the CSIC and that I develop in the CBM-SO (UAM/CSIC).

At the end of 2013, I joined to the Universidad de Sevilla with a Ramon y Cajal contract from the Spanish Science Ministry. Thanks to this tenure-track position and to the funding obtained from the Spanish Government (Plan Nacional, MINECO, BFU2013-44343-P) and the Universidad de Sevilla (Plan Propio) I have been trying to set up my own group/laboratory in the last 5 years. In this time, my research activity has been primarily centered on the study of the different roles of PolX polymerases in the maintenance of genome integrity in human cells, a work initially spotlighted in human Pol lambda and specially focused on its regulation by post-translational modifications. This research has provided interesting results (Sastre-Moreno et al. DNA Repair 2017 and unpublished results) and opened new research lines based on exciting and very promising preliminary results. My collaborative research with other research groups during this period has also been very productive, giving rise to research articles in top journals in the field. Since my integration in the Universidad de Sevilla, I have combined the research with teaching, mainly in the department of Bioquímica Vegetal y Biología Molecular.

My teaching activity has been focused on basic Biochemistry and Molecular Biology and has been positively evaluated by the US (1 quinquennial teaching activity approved by the Vicerrectorado de Profesorado). Likewise, the quality if my research has been recognized by the Spanish Agency for Quality Assessment and Accreditation (2 sexennials).

ORCID: 0000-0002-0039-3524
ResearcherID: A-1651-2015
Scopus: 7401444841
Dialnet: 3248618

Responsable de los siguientes proyectos:

  • Proyectos:
    • Bases Moleculares de la Formación de Translocaciones Cromosómicas Potencialmente Oncogénicas por Nhej. Papel y Regulación de las Polx Humanas (BFU2013-44343-P)
    • Bases Moleculares de Enfermedades Neurodegenerativas Ligadas a Acumulación Proteica: Papel de la Reparación de Roturas en el ADN (P11-CVI-7948)
  • Plan Propio:
    • INESTABILIDAD GENOMICA ASOCIADA A ROTURAS EN EL DNA (PP2017-8488)

Participa en los siguientes proyectos:

  • Proyectos:
    • Roturas de ADN Asociadas a Replicación y Reparación por Recombinación de Genomas Eucarióticos (BFU2010-16372 – Investigador)
    • Bases Genéticas y Moleculares del Origen de la Inestabilidad Genomica en Eucariotas (P09-CVI-4567 – Investigador)
    • Inestabilidad genómica (CSD2007-00015 – Investigador)
    • Genómica Funcional de la Interconexión Transcripción -Transporte de ARN (P07-CVI-02549 – Investigador)
    • Bases genéticas y moleculares de la inestabilidad genómica y su relación con la biogénesis de los mRNPs de eucariotas (BFU2006-05260 – Investigador)
    • Bases genéticas y moleculares del origen de la inestabilidad genética en eucariotas (EXC/2005/CVI-624 – Investigador)
    • Collision or progression: DNA replication fork traversal and RNAPII transcription termitation (BIO2003-07172 – Contratado)
  • Ayudas:
    • Incentivo al Grupo de Investigación BIO-102 (2011/BIO-102 – Investigador)
    • Incentivo al Grupo de Investigación BIO-102 (2010/BIO-102 – Investigador)
    • Ayuda a la Consolidación del Grupo de Investigación BIO-102 (2009/BIO-102 – Investigador)
    • Ayuda a la Consolidación del Grupo de Investigación BIO-102 (2008/BIO-102 – Investigador)
    • Ayuda a la Consolidación del Grupo de Investigación BIO-102 (2007/BIO-102 – Investigador)
    • Ayuda a la Consolidación del Grupo de Investigación CVI-102 (2006/CVI-102)
    • Ayuda a la Consolidación del Grupo de Investigación CVI-102 (2005/CVI-102)

Book Chapters/Capítulos en Libros

Gómez-González B, Ruiz JF, Aguilera A. (2011) Genetic and molecular analysis of mitotic recombination in Saccharomyces cerevisiae. Methods in Molecular Biology 745:151-72. doi: 10.1007/978-1-61779-129-1_10. Book chapter in DNA Recombination Methods and Protocols (Ed. Tsubouchi, Hideo)

 

Publications in Scientific Journals/Publicaciones en Revistas de Investigación

García-Rubio M, Aguilera P, Lafuente-Barquero J, Ruiz JF, Simon MN, Geli V, Rondón AG and Aguilera A (2018) Yra1-bound RNA–DNA hybrids cause orientation-independent transcription–replication collisions and telomere instability. Genes and Development, 32, 965-977. doi:10.1101/gad.311274.117.

Sastre-Moreno G, Pryor, JM, Díaz-Talavera, A, Ruiz JF, Ramsden, DA and Blanco, L. (2017) Polμ tumour variants decrease the efficiency and accuracy of NHEJ. Nucleic Acids Research, 45(17), 10018-10031. doi:10.1093/nar/gkx625.

Muñoz-Galván, S, García-Rubio, M, Ruiz JF, Pardo, B, Jimeno, S, Gómez-González, B and Aguilera, A. (2017) A role for Rrm3 in sister chromatid recombination upon replication-born DNA breakage. PLoS Genetics 13(5): e1006781.doi.org/10.1371/journal.pgen. 1006781.

Sastre-Moreno G, Pryor, JM, Moreno-Oñate, M, Herrero-Ruiz, AM, Cortés-Ledesma, F, Blanco, L, Ramsden, DA and Ruiz JF # (2017) (#corresponding author). Regulation of human Polλ by ATM-mediated phosphorylation during Non-Homologous End Joining. DNA Repair 51:31-45. DOI: 10.1016/j.dnarep.2017.01.004.

Ruiz JF #, Pardo B, Sastre-Moreno G, Aguilera A#, Blanco L# (2013) Yeast pol4 promotes tel1-regulated chromosomal translocations. PLoS Genetics 9(7): e1003656. (#corresponding authors). doi: 10.1371/journal.pgen.1003656

Ruiz JF, Gómez-González B, Aguilera A. (2011) AID induces double-strand breaks at immunoglobulin switch regions and c-MYC causing chromosomal translocations in yeast THO mutants. PLoS Genetics 7(2): e1002009. doi: 10.1371/journal.pgen. 1002009.

Ruiz JF, Gómez-González B, Aguilera A. (2009) Chromosomal translocations caused by either pol32-dependent or pol32-independent triparental break-induced replication. Molecular and Cellular Biology 29(20):5441-54. doi: 10.1128/MCB.00256-09.

Juárez R, Ruiz JF, Nick McElhinny SA, Ramsden D, Blanco L. (2006) A specific loop in human DNA polymerase mu allows switching between creative and DNA-instructed synthesis. Nucleic Acids Research 34(16):4572-82. doi: 10.1093/nar/gkl457.

Lucas D, Laín de Lera T, González MA, Ruiz JF, Domínguez O, Casanova JC, Martínez-A C, Blanco L, Bernad A. (2005) Polymerase mu is up-regulated during the T cell-dependent immune response and its deficiency alters developmental dynamics of spleen centroblasts. European Journal of Immunology 35(5):1601-11. doi: 10.1002/eji.200526015.

González-Barrera S, Sánchez A, Ruiz JF, Juárez R, Picher AJ, Terrados G, Andrade P, Blanco L. (2005) Characterization of SpPol4, a unique X-family DNA polymerase in Schizosaccharomyces pombe. Nucleic Acids Research 33(15):4762-74. doi: 10.1093/nar/gki780.

Ruiz JF, Lucas D, García-Palomero E, Saez AI, González MA, Piris MA, Bernad A, Blanco L. (2004) Overexpression of human DNA polymerase mu (Pol mu) in a Burkitt’s lymphoma cell line affects the somatic hypermutation rate. Nucleic Acids Research 32(19):5861-73. doi:10.1093/nar/gkh929.

Ruiz JF, Juárez R, García-Díaz M, Terrados G, Picher AJ, González-Barrera S, Fernández de Henestrosa, AR and Blanco L. (2003) Lack of sugar discrimination by human Pol mu requires a single glycine residue. Nucleic Acids Research 31(15):4441-9.  doi: 10.1093/nar/gkg637.

García-Díaz M, Ruiz JF, Juárez R, Terrados G and Blanco L. (2003) Are there mutator polymerases? Scientific World Journal. 3:422-31.

García-Díaz M, Bebenek K, Sabariegos R, Domínguez O, Rodríguez J, Kirchhoff T, García-Palomero E, Picher AJ, Juárez R, Ruiz JF, Kunkel TA, and Blanco L. (2002) DNA polymerase lambda, a novel DNA repair enzyme in human cells. Journal of Biological Chemistry 277(15):13184-91. doi 10.1074/jbc.M111601200.

Ruiz JF, Domínguez O, Laín de Lera T, Garcia-Díaz M, Bernad A, and Blanco L (2001) DNA polymerase mu, a candidate hypermutase? Philosophical Transactions of the Royal Society of London Series B Biological Sciences 356(1405):99-109. doi:10.1100/tsw.2003.32.

García-Díaz M, Domínguez O, López-Fernández LA, de Lera LT, Saníger ML, Ruiz JF, Párraga M, García-Ortiz MJ, Kirchhoff T, del Mazo J, Bernad A, Blanco L. (2000) DNA polymerase lambda (Pol lambda), a novel eukaryotic DNA polymerase with a potential role in meiosis. Journal of Molecular Biology 301(4):851-67. doi:10.1006/jmbi.2000.4005.

Domínguez O#, Ruiz JF #, Laín de Lera T, García-Díaz M, González MA, Kirchhoff T, Martínez-A C, Bernad A, Blanco L. (2000) DNA polymerase mu (Pol mu), homologous to TdT, could act as a DNA mutator in eukaryotic cells. EMBO J. 19(7): 1731-42 (# co-authors). doi: 10.1093/emboj/19.7.1731.

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Science Divulgation Articles/Publicaciones en Revistas de Divulgación

Ruiz JF, Sastre-Moreno G (2017) Identificada una nueva vía de regulación en la reparación de roturas de doble cadena en ADN de células humanas. En: Genética Médica News.. Vol. 4. Núm. 76. Pag. 17-19