Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates.
We have identified a regulator of sister chromatid cohesion in a screen for cell cycle-controlled proteins. This 35 kDa protein is degraded through anaphase-promoting complex (APC)-dependent ubiquitination in G1. The protein is nuclear in interphase cells, dispersed from the chromatin in mitosis, and interacts with the cohesin complex. In Xenopus embryos, overexpression of the protein causes failure to resolve and segregate sister chromatids in mitosis and an increase in the level of cohesin associated with metaphase chromosomes. In cultured cells, depletion of the protein causes mitotic arrest and complete failure of sister chromatid cohesion. This protein is thus an essential, cell cycle-dependent mediator of sister chromatid cohesion. Based on sequence analysis, this protein has no apparent orthologs outside of the vertebrates. We speculate that the protein, which we have named sororin, regulates the ability of the cohesin complex to mediate sister chromatid cohesion, perhaps by altering the nature of the interaction of cohesin with the chromosomes.
Rankin
Susannah
S
Systems Biology Department, Harvard Medical School, Boston, Massachusetts 02115, USA. susannah_rankin@hms.harvard.edu
Ayad
Nagi G
NG
Kirschner
Marc W
MW
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins; D002457:Cell Extracts / Q000737:chemistry / Q000235:genetics; D002842:Chromatids / Q000378:metabolism*; D002846:Chromatography, Affinity; D002868:Chromosomal Proteins, Non-Histone; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000737:chemistry; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013462:Sulfur Radioisotopes; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D014714:Vertebrates; D014981:Xenopus; D029867:Xenopus Proteins; D000097722:Cohesins
D048868:Adaptor Proteins, Signal Transducing; D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; D002457:Cell Extracts; D002868:Chromosomal Proteins, Non-Histone; D005656:Fungal Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D029867:Xenopus Proteins; D000097722:Cohesins; C500695:CDCA5 protein, human; C500696:Cdca5 protein, mouse; C500694:sororin, Xenopus