“The chromosome is at the heart of all genetic processes”
The chromosome is at the heart of all genetic processes with the programmed expression of its content, by either genetic or epigenetic mechanisms, being central to the development of an organism. The precise coordination between duplication and segregation of chromosomal DNA during the cell division cycle is required to ensure that daughter cells inherit a complete complement of genetic material. Therefore safeguarding chromosome integrity during the cell cycle is arguably one of the most important challenges faced by cells. Mistakes during DNA replication, repair or chromosome segregation can potentially drive tumourigenesis. Moreover, many anti-cancer drugs work by interfering with these processes.
The central aim of the group is to investigate the mechanisms that ensure the inheritance of eukaryotic genomes during cell division. We are interested in two key events that mark the reproductive life of the cell: the accurate duplication of the genetic material and its faithful distribution to daughter cells. Our approach is to study factors known to play fundamental roles in key aspects of these two processes. These include the SMC complexes, cohesin, condensin and Smc5/6 and the mitotic exit phosphatase Cdc14.
CatC* (positively supercoiled) catenated plasmids are preferentially decatenated by topoisomerase II in vitro.
McAleenan, A., Clemente-Blanco, A., Cordon-Preciado, V., Sen, N., Esteras, M., Jarmuz, A., & Aragón, L. (2013). Post-replicative repair involves separase-dependent removal of the kleisin subunit of cohesin. Nature, 10;493(7431):250-4
Baxter, J., Sen, N., Martı́nez, V. L., De Carandini, M. E. M., Schvartzman, J. B., Diffley, J. F. X., & Aragón, L. (2011). Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes. Science, 331(6022), 1328–1332.
Clemente-Blanco, A., Mayan-Santos, M., Schneider, D. A., Machin, F., Jarmuz, A., Tschochner, H., & Aragon, L. (2009). Cdc14 inhibits transcription by RNA polymerase i during anaphase. Nature, 458(7235), 219–222.
De Piccoli, G., Cortes Ledesma, F., Ira, G., Torres Rosell, J., Farmer, S., Hwang, H. J., Machin, F., Ceschia, A., McAleenan, A., Cordon Preciado, V., Clemente Blanco, A., Vilella Mitjana, F., Ullal, P., Jarmuz, A., Leitao, B., Bressan, D., Dotiwala, F., Papusha, A., Zhao, X., Myung, K., Haber, J. E., Aguilera, A., & Aragón, L. (2006). Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nature Cell Biology, 8, 1032–1034.
Torres Rosell, J., De Piccoli, G., Cordon Preciado, V., Farmer, S., Jarmuz, A., Machin, F., Pasero, P., Lisby, M., Haber, J. E., & Aragón, L. (2007). Anaphase onset before complete DNA replication with intact checkpoint responses. Science, 315, 1411–1415.
Machı́n, F., Torres Rosell, J., De Piccoli, G., Carballo, J. A., Cha, R. S., Jarmuz, A., & Aragón, L. (2006). Transcription of ribosomal genes can cause nondisjunction. Journal of Cell Biology, 173, 893–903.