CENTRO DE INVESTIGACION DEL CANCER

  • Laboratorio 8

Andrés Avelino Bueno Núñez

Genetic stability: Genome replication and DNA damage tolerance


Biography

Avelino Bueno received his Ph.D. from the Department of Microbiology at the University of Salamanca (USAL, Spain) in 1988 thanks to the support of a PFPI fellowship from the Spanish Ministry of Science and Education. His doctoral dissertation summarized the molecular characterization of genes encoding exocellular carbohydrolases from Bacillus species, a scientific project run under the supervision of Professors Francisco del Rey, Julio Rodriguez-Villanueva and Tomás González-Villa.

From 1989 to 1991, he carried out postdoctoral training in the cell cycle field in Dr. Paul Russell’s group at the Scripps Research Foundation in La Jolla (California) thanks to the support of a Fulbright Posdoctoral Fellowship. He remained there as a senior postdoc until the end of 1992 as a R+D employee of The Scripps Research Institute (TSRI). During this period of time he characterized genes involved in cell cycle regulation encoding key proteins such as the DNA replication initiator Cdc6, the G2/M kinase Swe1, and those encoding G2 and G1 cyclins Cig1 and Cig2 in yeast models (Cell 1991, EMBO Journal 1992, Mol Cell Biol 1993 and J Biol Chem 1994). Avelino Bueno developed at TSRI a strong interest in DNA replication control mechanisms in the cell cycle field before starting his own research group at the beginning of 1993.

Avelino Bueno formed his own lab at the University of Salamanca with a clear focus on specific DNA replication control mechanisms involving the initiator protein Cdc6/Cdc18, the Rad53/Chk2 checkpoint kinase, as well as phosphatases Cdc14/Flp1, using as experimental models both budding and fission yeast (JBC 99, JCS 99, JBC, 00, Nature 01, JCS 01 and 04, Genes&Dev 05, NARes 06, MBC 08), later to expand to cell cycle phosphatases Cdc14A and Cdc14B in animal cell models in collaboration with Dr. María Sacristán (JBC 05, CC 06/08/11, JBC 10, MBC 12, SR, under review). Initially (1993-2000) his group was first established at the IMB Research Institute (USAL-CSIC) thanks to a tenured associated professorship position to later move to the Cancer Research Institute (IMBCC USAL-CSIC), in 2001, as a full professor of Microbiology. In the last seven years his lab has been particularly interested in the mechanism reverting PCNA ubiquitylation. In particular, his research team has been focused in understanding the biological meaning of PCNA deubiquitylation during S-phase to uncover the consequences of altering this evolutionarily conserved eukaryotic mechanism (BST 10, PLoS Genetics 12, PLoS ONE 13, Scientific Reports 16).

It is important to mention that throughout the years, Dr. Bueno has establshed productive scientific collaborations with Spanish and International Research Groups (i.e.: Sergio Moreno, IBMCC; Pedro San Segundo, IBFG; Rodrigo Bermejo, CIB; Viesturs Simanis, ISREC-Lausanne; Karim Labib, Dundee University; Luis Aragón, MRC-London). Finally, it is also noteworthy to acknowledge that, from 2012 to 2016, Dr. Bueno has been Director/Coordinator of the Master Degree in Biology and Clinic of Cancer, official title of the University of Salamanca, a key part of the Postgraduate School of the Cancer Research Institute in Salamanca (IMBCC USAL-CSIC)

1984-1988 PhD studies. Department of Microbiology, University of Salamanca. IMB, joint research center CSIC/University of Salamanca.

1989-1992 Post-doctoral Fulbright Fellow in Paul Russell’s lab (Department of Molecular Biology) at “The Scripps Research Institute” in La Jolla, California (USA).

1993-2002 Assistant Professor of Microbiology, University of Salamanca. Member of IMB, joint research center CSIC/University of Salamanca.

2002-present. Professor of Microbiology, Department of Microbiology and Genetics, University of Salamanca. Member of IBMCC at the Cancer Research Center of the University of Salamanca.

Andrés Avelino Bueno Núñez
Contact

Dr. Avelino Bueno Núñez
Catedrático de Microbiología.
Laboratorio Nº 5

923 294 805
abn(arroba)usal(.)es

Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)
Campus Universitario Miguel de Unamuno s/n
37007 Salamanca
SPAIN-

Areas of Research

Reversible processes in cell cycle control: Dynamic ubiquitylation and deubiquitylation of PCNA during S-phase

Fidelity in chromosome duplication and segregation is indispensable for maintaining genomic stability and the perpetuation of life. Challenges to genome integrity jeopardize cell survival and are at the root of different types of pathologies, such as cancer. Living organisms are constantly exposed to endogenous and exogenous DNA damage, a major threat to genomic stability. Cells are particularly sensitive to damage during DNA replication because the stringent nature of replicative DNA polymerases cannot accommodate damaged bases and, consequently, DNA synthesis is blocked with potential deleterious effects. To deal with base damage during replication all three domains of life have evolved DNA damage tolerance mechanisms (DDT) that allow them to circumvent DNA lesions allegedly to ensure progression of replication forks. Tolerance to DNA damage is based on translesion DNA synthesis (TLS), a bypass mechanism that allows cells to overcome DNA base lesions that interfere with progression of replicative DNA polymerases. We are interested in the analysis of control mechanisms that regulate a processive DNA replication during S-phase in the cell division cycle. The model systems used in our research projects are mainly S.cerevisiae and S.pombe yeast. Working with these two model systems give us a real perspective of what control mechanisms are really important, therefore conserved, throughout evolution in the eukaryotic cell cycle. Along this line and as an example, the comparative work that we have done with PCNA deubiquitylation in S.pombe suggested a dynamic process ensuring appropriate progression through S-phase. This evidence hinted a secondary experimental approach in S.cerevisiae to uncover that PCNA-DUBs downregulate DDT at replication forks (Gallego-Sánchez et al., 2012; Álvarez et al., 2016 Scientific Reports; Álvarez et al 2019 Cell Reports). We are currently focusing our research on PCNA-DUBs proteomics trying to understand patterns of interactions and functionality of this ubiquitin-proteases. Additionally, we are starting a new research project on mechanisms regulating DNA damage tolerance based on the asymmetric localisation of PCNA-DUBs at nascent DNA.

We are currently working on the following research projects:

We are focused to understanding how processive DNA synthesis is ensured in the presence of damaged templates and whether PCNA-DUBs asymmetric localisation at replication forks have any functional implications for DDT control.

I. Analysis of PCNAK164 ubiquitin-proteases (PCNA-DUBs) as regulatory replisome components.

II. Testing asymmetry in DNA damage tolerance regulation at replication forks.

Working model for DDT suppression at replication forks through Ubp1-, Ubp10- and Ubp12-mediated PCNAK164 deubiquitylation

Projects
  • JUNTA DE CASTILLA Y LEON (2022-2000)

    Análisis del papel de reguladores del ciclo celular en respuesta al daño en el genoma causado por agentes genotóxicos.

  • MINISTERIO DE CIENCIA Y TECNOLOGIA (2015-2000)

    Controles de entrada en G1 y de inicio de fase S en el ciclo de división celular de levaduras.

  • Junta de Castilla y León (2003-2000)

    Reguladores del ciclo celular en la respuesta a estres replicativo y/o genotóxico: estudio de cdc14 y chk2 en levaduras y celulas animales

  • JUNTA DE CASTILLA Y LEON (2001-2000)

    Relación entre los controles reguladores de la entrada en G1 y del inicio de la fase S en el ciclo celular eucariota.

  • MINISTERIO DE CIENCIA Y TECNOLOGÍA (2001-2000)

    PROTEOMICA DE PROTEIN-FOSFATASAS REGULADORAS DEL CICLO CELULAR EUCARIÓTICO

  • Ministerio de Economía Y Competitividad (2001-2000)

    Estudio de procesos reversibles en el control del ciclo celular: fosforilación por CDK en mitosis y ubiquitina de PCNA

  • Ministerio de Ciencia y Tecnología (2001-2000)

    REGULADORES DEL CICLO DE DIVISION CELULAR EN LA RESPUESTA A ESTRES GENOTÓXICO EN LEVADURAS

  • MINISTERIO DE CIENCIA E INNOVACION (2001-2000)

    MECANISMOS DE REGULACION DE LA RESPUESTA A ESTRES REPLICATIVO EN LEVADURAS

  • BFU2015-69709-P (2001-2031)

    Reversible processes in cell cycle control: PCNA ubiquitylation and protein phosphorylation in response to DNA damage    

Junta de Castilla y León Ministerio de economía y competitividad Fondo europeo de desarrollo regional
Publications

(*) Means equal contribution as senior authors.



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cdc25 M-phase inducer.

Millar J, McGowan C, Jones R, Sadhu K, Bueno A, Richardson H, Russell P, 
Cold Spring Harb Symp Qua; 1991; 56(); 577-84; 1819507


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  • Esmeralda Alonso Rodríguez Esmeralda Alonso Rodríguez

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  • Andrés Avelino Bueno Núñez Andrés Avelino Bueno Núñez

    Andrés Avelino Bueno Núñez

    Genetic stability: Genome replication and DNA damage tolerance

    Telf.:

    Fax:

    Email: abn@usal.es


    Contact

    Dr. Avelino Bueno Núñez
    Catedrático de Microbiología.
    Laboratorio Nº 5

    923 294 805
    abn(arroba)usal(.)es

    Centro de Investigación del Cáncer (Universidad de Salamanca-CSIC)
    Campus Universitario Miguel de Unamuno s/n
    37007 Salamanca
    SPAIN


    Biography

    Avelino Bueno received his Ph.D. from the Department of Microbiology at the University of Salamanca (USAL, Spain) in 1988 thanks to the support of a PFPI fellowship from the Spanish Ministry of Science and Education. His doctoral dissertation summarized the molecular characterization of genes encoding exocellular carbohydrolases from Bacillus species, a scientific project run under the supervision of Professors Francisco del Rey, Julio Rodriguez-Villanueva and Tomás González-Villa.

    From 1989 to 1991, he carried out postdoctoral training in the cell cycle field in Dr. Paul Russell’s group at the Scripps Research Foundation in La Jolla (California) thanks to the support of a Fulbright Posdoctoral Fellowship. He remained there as a senior postdoc until the end of 1992 as a R+D employee of The Scripps Research Institute (TSRI). During this period of time he characterized genes involved in cell cycle regulation encoding key proteins such as the DNA replication initiator Cdc6, the G2/M kinase Swe1, and those encoding G2 and G1 cyclins Cig1 and Cig2 in yeast models (Cell 1991, EMBO Journal 1992, Mol Cell Biol 1993 and J Biol Chem 1994). Avelino Bueno developed at TSRI a strong interest in DNA replication control mechanisms in the cell cycle field before starting his own research group at the beginning of 1993.

    Avelino Bueno formed his own lab at the University of Salamanca with a clear focus on specific DNA replication control mechanisms involving the initiator protein Cdc6/Cdc18, the Rad53/Chk2 checkpoint kinase, as well as phosphatases Cdc14/Flp1, using as experimental models both budding and fission yeast (JBC 99, JCS 99, JBC, 00, Nature 01, JCS 01 and 04, Genes&Dev 05, NARes 06, MBC 08), later to expand to cell cycle phosphatases Cdc14A and Cdc14B in animal cell models in collaboration with Dr. María Sacristán (JBC 05, CC 06/08/11, JBC 10, MBC 12, SR, under review). Initially (1993-2000) his group was first established at the IMB Research Institute (USAL-CSIC) thanks to a tenured associated professorship position to later move to the Cancer Research Institute (IMBCC USAL-CSIC), in 2001, as a full professor of Microbiology. In the last seven years his lab has been particularly interested in the mechanism reverting PCNA ubiquitylation. In particular, his research team has been focused in understanding the biological meaning of PCNA deubiquitylation during S-phase to uncover the consequences of altering this evolutionarily conserved eukaryotic mechanism (BST 10, PLoS Genetics 12, PLoS ONE 13, Scientific Reports 16).

    It is important to mention that throughout the years, Dr. Bueno has establshed productive scientific collaborations with Spanish and International Research Groups (i.e.: Sergio Moreno, IBMCC; Pedro San Segundo, IBFG; Rodrigo Bermejo, CIB; Viesturs Simanis, ISREC-Lausanne; Karim Labib, Dundee University; Luis Aragón, MRC-London). Finally, it is also noteworthy to acknowledge that, from 2012 to 2016, Dr. Bueno has been Director/Coordinator of the Master Degree in Biology and Clinic of Cancer, official title of the University of Salamanca, a key part of the Postgraduate School of the Cancer Research Institute in Salamanca (IMBCC USAL-CSIC)

    1984-1988 PhD studies. Department of Microbiology, University of Salamanca. IMB, joint research center CSIC/University of Salamanca.

    1989-1992 Post-doctoral Fulbright Fellow in Paul Russell’s lab (Department of Molecular Biology) at “The Scripps Research Institute” in La Jolla, California (USA).

    1993-2002 Assistant Professor of Microbiology, University of Salamanca. Member of IMB, joint research center CSIC/University of Salamanca.

    2002-present. Professor of Microbiology, Department of Microbiology and Genetics, University of Salamanca. Member of IBMCC at the Cancer Research Center of the University of Salamanca.

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  • Lorena Díaz Ajenjo Lorena Díaz Ajenjo

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    Manuel Jacob Fuentes Matos

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  • María de la Paz Sacristán Martín María de la Paz Sacristán Martín

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    Reversible phosphorylation processes in cell cycle control: role of Cdc14 protein phosphatases

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  • Javier Zamarreño Lozano Javier Zamarreño Lozano

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