The role of the Smc5/6 complex and the Mms21 SUMO Ligase in the maintenance of genomic integrity
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The Structural Maintenance of Chromosomes (SMC) Smc5/6 complex has a poorly understood function in chromosome repair and segregation. In this study, we show that the dissolution of DNA-mediated connections requires the Smc5/6 complex. smc5/6 mutants fail to remove chromosome linkages, leading to gross
chromosome segregation defects. Besides, we show that these connections are mainly due to the accumulation of recombination intermediates and replication forks, and are not mediated by catenanes. Our assay demonstrates that the Smc5/6 complex is capable of promoting chromosome disjunction in metaphase-arrested cells, thus restoring chromosome segregation. The Smc5/6 complex is also the docking site for a SUMO E3 ligase, a feature that highlights its potential signalling skills. Our initial characterization of the lysines targeted by SUMO suggests that Smc5 SUMOylation is required for its recruitment to sites of DNA damage and proper DNA repair. The activity of the SUMO ligase is induced in response to DNA damage, a phenomenon that requires the presence of an active homologous recombination pathway. Our results also show that the SUMO ligase domain is required for chromosome disjunction, and indicate that the Smc5/6-Mms21 complex operates as a giant SUMO ligase.
- Tesis Doctorals