Molecular Genetics

Sister chromatid cohesion and chromatid condensation are temporally separate processes.

Facts

• Though many cohesive links between sister chromatids Must be broken during chromosome condensation especially at centromeres, a few remain to keep the sister chromatids apposed to one another. The last links must be broken during the metaphase-anaphase transition.
• 13S condensin is phosphorylated only during mitosis. The phosphorylated form is more active in stimulating supercoiling and knotting activity. The phosphorylating enzyme is thought to be the cyclin-dependent kinase cdc2p.
• Condensin binds to chromatin in mitotic phase extracts of Xenopus cells, but not in extracts of other phases.
• A protein complex, called the cyclosome or anaphase promoting complex is a ubiquitinating enzyme that tags a variety of proteins for destruction. Among the targets of the cyclosome is Pds1/Cut2/securin. This protein binds to Cut1/Esp1/separin preventing its activity. Liberated Cut1/Esp1/separin destroys Scc1p, a polypeptide of the 14S cohesin complex.

                                          APC
                                           |
Separin--Securin <---> Separin + Securin  ---> U-Securin --> degr.
  inactive             active|
                             |
             Cohesin Scc1p ----> degr.

Interpretations

• Final separation of sister chromatids may be caused by activation of the cyclosome which destroys securin, leading to destruction of cohesin by separin.
• Many protein-protein interactions are involved in chromosome separation, suggesting that more complex interactions also play a role.

Further information

• Phosphorylation of the Scc1p subunit of cohesin by a polo/cdc5 kinase increases its susceptibility to destruction by separin (ref).
• Other molecules involved in chromatin segregation include condensins, monopolins, microtubule motors, and regulatory proteins (rev).

This is page 13613 of Molecular Genetics by Ulrich Melcher, © 2001