| Research Team | Research Interest | Projects | Publications | Opportunities |

RESEARCH TEAM

PEDRO A. SAN SEGUNDO NIETO. Research Scientist CSIC.

FRANCISCO M. CONDE PÉREZ. Postdoctoral.
ESTHER REFOLIO CARNICERO. Predoctoral (FPI).
DAVID ONTOSO PICÓN. Predoctoral (JAE/CSIC).

ISABEL ACOSTA GÓMEZ. Technician.

RESEARCH INTEREST

1) Meiotic cell cycle checkpoints

Meiosis is a special kind of cell division, which generates haploid gametes from diploid parental cells; therefore it is an essential process in the life cycle of sexually reproducing organisms. During the meiotic cell cycle, a complex series of events result in the reduction of the number of chromosomes by half. Like mitotically dividing cells, meiotic cells possess surveillance mechanisms or ‘checkpoints’ that control and ensure proper distribution of the genetic material to progeny.

We are interested in the study of the so-called ‘pachytene checkpoint’ or ‘meiotic recombination checkpoint’, which blocks or delays meiotic cell cycle progression in response to defects in recombination or chromosome synapsis, thus preventing aberrant chromosome segregation and formation of aneuploid gametes.

In humans, errors in meiotic chromosome segregation are the leading cause of spontaneous abortions; those aneuploid embryos that survive present genetic diseases, such as for example Down’s syndrome.

2) Genome stability

Eukaryotic cells react to the presence of genome injuries by activating DNA repair mechanisms and signal transduction pathways that delay cell cycle progression until damage has been repaired. In mammals, inability to properly respond to DNA damage causes genetic instability associated to tumor development.

Detection, signaling and repair of genome injuries, as well as meiotic recombination processes, do not take place on the naked DNA, but in the context of highly organized chromatin. Thus, it is expected that regulatory factors of chromatin structure play important roles in these processes.

We are interested in the study of the contribution of certain histone modifications (methylation, phosphorylation…) to the maintenance of genomic integrity.

We use the yeast Saccharomyces cerevisiae as a model of study. Generally, checkpoint controls are evolutionary conserved; therefore, studies in yeasts are relevant to the fundamentals of molecular mechanisms that contribute to maintain genomic stability in higher eukaryotes in both mitotic and meiotic cells.


RECENT GRANTS

Mecanismos de vigilancia (“checkpoints”) del ciclo celular meiótico.
Proyecto del Plan Nacional de Investigación del Ministerio de Ciencia y Tecnología. Ref. BMC2002-00121.
Duración: 1/12/2002 hasta 1/12/2005.
Investigador Principal: Dr. Pedro A. San Segundo

Estudio de la contribución de la proteina Dot1 al mantenimiento de la estabilidad genómica durante el ciclo celular mitótico y meiótico.
Junta de Castilla y León. Ref. SA118/03
Duración: 1/1/2003 hasta: 31/12/2004.
Investigador Principal: Dr. Pedro A. San Segundo

Estudio funcional del “checkpoint” de recombinación meiótica en levaduras mediante análisis proteómico.
Proyecto del Plan Nacional de Investigación del Ministerio de Ciencia y Tecnología.. (Acción Estratégica de Genómica y Proteómica). Ref. GEN2003-20243-C08-06
Duración: 01/09/2004 hasta 31/08/2007.
Investigador Principal: Dr. Pedro A. San Segundo

Estudio de la contribución de factores moduladores de la cromatina al mantenimiento de la estabilidad genómica durante el ciclo celular mitótico y meiótico.
Junta de Castilla y León. Ref. SA002A05
Duración: 01/01/2005 hasta 31/012/2006.
Investigador Principal: Dr. Pedro A. San Segundo

Mecanismos de Vigilancia (“Checkpoints”) del Ciclo Celular Meiótico y Respuesta Celular a Daño en DNA.
Proyecto del Plan Nacional de Investigación del Ministerio de Educación y Ciencia. Ref. BFU2005-00955/BMC
Duración, 2006-2008.
Investigador Principal: Dr. Pedro A. San Segundo

Estudio de la respuesta celular al daño en el DNA durante el ciclo mitótico y meiótico.
Proyecto del Plan Nacional de Investigación del Ministerio de Ciencia e Innovación. Ref. BFU2008-01014/BMC
Duración: 01/01/09 a 31/12/09
Investigador Principal: Dr. Pedro A. San Segundo

Respuesta celular al daño en el DNA durante el ciclo mitótico y meiótico.
Proyecto del Plan Nacional de Investigación del Ministerio de Ciencia e Innovación. Ref. BFU2009-07159
Duración: 01/01/2010 a 31/12/2012
Investigador Principal: Dr. Pedro A. San Segundo

Regulación epigenética del mantenimiento de la estabilidad genómica durante el ciclo celular mitótico y meiótico
Proyecto de Investigación de la Fundación Ramón Areces
Duración: 2010-2012
Investigador Principal: Dr. Pedro A. San Segundo

RELEVANT PUBLICATIONS

GALLEGO-SANCHEZ A, CONDE F, SAN SEGUNDO P, BUENO A. 2010. Control of PCNA deubiquitylation in yeast. Biochem Soc Trans. 38:104-9. link

CONDE, F., REFOLIO. E., CORDON-PRECIADO, V., CORTES-LEDESMA, F., ARAGON, L. AGUILERA, A., SAN-SEGUNDO, P. 2009. The Dot1 Histone Methyltransferase and the Rad9 Checkpoint Adaptor Contribute to Cohesin-Dependent Double-Strand Break Repair by Sister Chromatid Recombination in Saccharomyces cerevisiae. Genetics 182:437-446. link

LIVIA PEREZ-HIDALGO, SERGIO MORENO and PEDRO A. SAN-SEGUNDO. 2008. The Fission Yeast Meiotic Checkpoint Kinase Mek1 Regulates Nuclear Localization of Cdc25 by Phosphorylation. Cell Cycle. 7:3720-3730. Link

CONDE, F.M., SAN-SEGUNDO, PA. 2008. Role of Dot1 in the Response to Alkylating DNA Damage in Saccharomyces cerevisiae: Regulation of DNA Damage Tolerance by the Error-Prone Polymerases Pol{zeta}/Rev1. Genetics. 179: 1197-1210. Link

MARTÍN-CASTELLANOS, C., M. BLANCO, A. E. ROZALÉN, L. PÉREZ-HIDALGO, A. I. GARCÍA, F. CONDE, J. MATA, C. ELLERMEIER, L. DAVIS, P. SAN-SEGUNDO, G. R. SMITH, AND S. MORENO. 2005. A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events. Current Biology 15(22):2056-62.Link

PERERA D, PEREZ-HIDALGO L, MOENS PB, REINI K, LAKIN N, SYVAOJA JE, SAN-SEGUNDO PA, FREIRE R. 2004. TopBP1 and ATR colocalization at meiotic chromosomes: role of TopBP1/Cut5 in the meiotic recombination checkpoint.
Mol Biol Cell. 4:1568-79. Link

PEREZ-HIDALGO L, MORENO S, SAN-SEGUNDO PA. 2003 Regulation of meiotic progression by the meiosis-specific checkpoint kinase Mek1 in fission yeast. J Cell Sci. 116(Pt 2):259-71. Link

SAN-SEGUNDO PA, ROEDERr GS.2000. Role for the silencing protein Dot1 in meiotic checkpoint control.
Mol Biol Cell.10:3601-15. Link

SAN-SEGUNDO PA, Roeder GS. 1999. Pch2 links chromatin silencing to meiotic checkpoint control.
Cell. 3:313-24. Pubmed

UFANO S, SAN-SEGUNDO P, del REY F, VAZQUEZ DE ALDANA CR. 1999. SWM1, a developmentally regulated gene, is required for spore wall assembly in Saccharomyces cerevisiae. Mol Cell Biol.3:2118-29. Pubmed



OPPORTUNITIES

If you are interested in any of our work and would like to join the group as a graduate student or postdoctoral fellow, then please write to PEDRO A. SAN SEGUNDO (pedross@usal.es) and include a copy of your current C.V.