Jordi Torres-Rosell
The most fundamental process regulated by mitotic cells is the faithful replication and segregation of the genetic material. Failure to maintain the integrity of the genome often leads to the death of the cell or to chromosome aberrations, a hallmark of cancer cells.

Three essential complexes of the Structural Maintenance of Chromosomes (SMC) family, cohesin, condensin and the Smc5/6 complex, play key roles in maintaining genome integrity during the cell cycle. The best characterized complex in the family is Cohesin, which maintains sister chromatid cohesion from S phase until anaphase, and also in response to DNA damage. Condensin is involved in chromosome shaping through chromatid condensation and resolution. The function of the Smc5/6 complex seems to be at the crossroads of chromosome replication, segregation and DNA repair: smc5/6 mutants display increased frequency of gross chromosomal rearrangements, defects in sister chromatid recombination, failure to complete genome replication and chromosome non-disjunction. In contrast to other SMC complexes, one of its subunits is a SUMO-ligase, and a second one is a ubiquitin-ligase, what suggests that Smc5/6 might have signaling competencies apart from a structural role. Intriguingly, all three SMC complexes are SUMOylated during an unperturbed cell cycle and after DNA damage. In most cases, this modification depends on the SUMO-ligase associated with the Smc5/6 complex.

Our main research goals are (i) to understand the role of Smc5/6 in chromosome disjunction after DNA damage; (ii) to elucidate how modification by SUMO regulates SMC activity; and (iii) to identify what mechanisms are involved in the activation of the Smc5/6-associated SUMO-ligase. For this purpose, we are using budding yeast as a model organism, and different tools to alter SUMOylation of SMC complexes.

For further information:

Figure 1:A. smc5/6 mutants fail to segregate nuclei after a pulse of DNA damage. Nuclear missegregation is observed in smc5/6 mutant cells that enter a second cell cycle (evidenced by appearance of a new bud). B. FACS profile indicates that smc5/6 mutants also generate aneuploid progeny (red arrow) after DNA damage. C. Working model: Smc5/6 signals the resolution of DNA linkages (recombination intermediates and unfinished replication structures) to allow chromosome segregation.