First name
Lucia
Last name
Massari
Year of Study
Research Center
Thesis Title
Complete resolution of sister chromatid intertwines requires the Polo-like kinase Cdc5 and the phosphatase Cdc14 in budding yeast
Thesis Abstract
During mitosis the newly replicated genetic material, organized in sister chromatids, is
equally subdivided into the daughter cells through a fine-regulated process called
chromosome segregation. Sister chromatids are held together and identified as sisters by
cohesin. At the metaphase-to-anaphase transition, when all chromatids are correctly
attached to the spindle, cohesin is cleaved and chromosome segregation initiates. Beside
cohesin, all linkages between sister chromatids need to be removed to allow for their
complete separation. Additional linkages include DNA linkages (or sister chromatid
intertwines, SCIs), such as recombination intermediates and DNA catenanes.
In Saccharomyces cerevisiae a mutant that lacks the activities of the Polo-like
kinase Cdc5 and the phosphatase Cdc14, two major mitotic regulators, has been identified
that proved to be particularly suitable for studying SCIs that persist in mitosis. The cdc5
cdc14 double mutant arrests with short and stable mitotic spindles and unseparated nuclei,
despite having cleaved cohesin. In addition to having a spindle elongation defect, these
cells are also impaired in the resolution of cohesin-independent linkages between
chromatids.
We found that these linkages mostly consist of DNA catenanes, that persist in cdc5
cdc14 cells at their terminal arrest and that are sufficient to counteract spindle elongation.
Our results suggest that Cdc5 is required for their resolution.
This finding, together with the knowledge that Cdc5 promotes Cdc14 activation
and that both proteins are essential for spindle elongation and mitotic exit, allows us to
speculate that they coordinate different aspects of chromosome segregation to guarantee
genome integrity throughout mitosis.
equally subdivided into the daughter cells through a fine-regulated process called
chromosome segregation. Sister chromatids are held together and identified as sisters by
cohesin. At the metaphase-to-anaphase transition, when all chromatids are correctly
attached to the spindle, cohesin is cleaved and chromosome segregation initiates. Beside
cohesin, all linkages between sister chromatids need to be removed to allow for their
complete separation. Additional linkages include DNA linkages (or sister chromatid
intertwines, SCIs), such as recombination intermediates and DNA catenanes.
In Saccharomyces cerevisiae a mutant that lacks the activities of the Polo-like
kinase Cdc5 and the phosphatase Cdc14, two major mitotic regulators, has been identified
that proved to be particularly suitable for studying SCIs that persist in mitosis. The cdc5
cdc14 double mutant arrests with short and stable mitotic spindles and unseparated nuclei,
despite having cleaved cohesin. In addition to having a spindle elongation defect, these
cells are also impaired in the resolution of cohesin-independent linkages between
chromatids.
We found that these linkages mostly consist of DNA catenanes, that persist in cdc5
cdc14 cells at their terminal arrest and that are sufficient to counteract spindle elongation.
Our results suggest that Cdc5 is required for their resolution.
This finding, together with the knowledge that Cdc5 promotes Cdc14 activation
and that both proteins are essential for spindle elongation and mitotic exit, allows us to
speculate that they coordinate different aspects of chromosome segregation to guarantee
genome integrity throughout mitosis.
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