Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair

Background: In mammals, proteins containing BIR domains (LAPs and survivin) are implicated in inhibiting apoptosis and sister chromatid separation. In the nematode, Bir1 is required for a proper localization of aurora kinase, which moves from the mitotic chromosome in metaphase to the spindle midzon e in anaphase as a passenger. Fission yeast Bir1/Pbh1 is essential for norm al mitosis. Results: A temperature sensitive mutant cut17-275 exhibits the defect in co ndensation and spindle elongation at 36 degreesC, while securin is degraded . Gene cloning shows that the cut17(+) gene is identical to bir1(+)/pbh1(+) . At 26 degreesC, cut17-275 is LTV sensitive as the repair of DNA damage is severely compromised. Bir1/Cut17 is a nuclear protein in interphase, which is then required for recruiting condensin to the mitotic nucleus, and conc entrates to form a discrete number of dots from prometaphase to metaphase. Once the chromatids are separated, Bir1/Cut17 no longer binds to kinetochor es and instead moves to the middle of spindle. Chromatin immunoprecipitatio n suggested that Bir1/Cut17 associates with the outer repetitious centromer e region in metaphase. Following the initiation of anaphase the protein swi tches from being a chromosomal protein to a spindle protein. This transit i s stringently regulated by the state of sister chromatid cohesion proteins Mis4 and Rad21. Ark1, is an aurora kinase homologue whose mitotic distribut ion is identical to, and under the control of Bir1/Cut17. Conclusions: Bir1/Cut17 and Ark1 act as 'passengers' but they may play a ma in role as a recruitment factor, essential for condensation, spindle elonga tion and DNA repair. Bir1/Cut17 should have roles both in mitotic and in in terphase chromosome. The proper location of Ark1 requires Bir1/Cut17, and t he mitotic localization of Bir1/Cut17 requires sister cohesion.