A conserved motif at the C terminus of sororin is required for sister chromatid cohesion.
Sororin is a positive regulator of sister chromatid cohesion that interacts with the cohesin complex. Sororin is required for the increased stability of the cohesin complex on chromatin following DNA replication and sister chromatid cohesion during G(2). The mechanism by which sororin ensures cohesion is currently unknown. Because the primary sequence of sororin does not contain any previously characterized structural or functional motifs, we have undertaken a structure-function analysis of the sororin protein. Using a series of mutant derivatives of sororin, we show that the ability of sororin to bind to chromatin is separable from both its role in sister chromatid cohesion and its interaction with the cohesin complex. We also show that derivatives of sororin with deletions or mutations in the conserved C terminus fail to rescue the loss-of-cohesion phenotype caused by sororin RNAi and that these mutations also abrogate the association of sororin with the cohesin complex. Our data suggest that the interaction of the highly conserved motif at the C terminus of sororin with the cohesin complex is critical to its ability to mediate sister chromatid cohesion.
Program in Cell Cycle and Cancer Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Frank M
FM
Wu
Judy V
JV
Nguyen
Susannah
S
Rankin
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D000097722:Cohesins
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000097722:Cohesins; C500695:CDCA5 protein, human