Cohesin is dispensable for centromere cohesion in human cells.
BACKGROUND
Proper regulation of the cohesion at the centromeres of human chromosomes is essential for accurate genome transmission. Exactly how cohesion is maintained and is then dissolved in anaphase is not understood.


RESULTS
We have investigated the role of the cohesin complex at centromeres in human cells both by depleting cohesin subunits using RNA interference and also by expressing a non-cleavable version of the Rad21 cohesin protein. Rad21 depletion results in aberrant anaphase, during which the sister chromatids separate and segregate in an asynchronous fashion. However, centromere cohesion was maintained before anaphase in Rad21-depleted cells, and the primary constrictions at centromeres were indistinguishable from those in control cells. Expression of non-cleavable Rad21 (NC-Rad21), in which the sites normally cleaved by separase are mutated, resulted in delayed sister chromatid resolution in prophase and prometaphase, and a blockage of chromosome arm separation in anaphase, but did not impede centromere separation.


CONCLUSIONS
These data indicate that cohesin complexes are dispensable for sister cohesion in early mitosis, yet play an important part in the fidelity of sister separation and segregation during anaphase. Cleavage at the separase-sensitive sites of Rad21 is important for arm separation, but not for centromere separation.
Díaz-Martínez
Laura A
LA
Department of Genetics, Cell Biology and Development, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Giménez-Abián
Juan F
JF
Clarke
Duncan J
DJ
D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002503:Centromere / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008938:Mitosis / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D015739:Nocodazole; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase; D000097722:Cohesins