Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage

TY - JOUR

T1 - Sister chromatid separation and chromosome re-duplication are regulated by different mechanisms in response to spindle damage

AU - Alexandru, Gabriela

AU - Zachariae, Wolfgang

AU - Schleiffer, Alexander

AU - Nasmyth, Kim

PY - 1999

Y1 - 1999

N2 - In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2, Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC), Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APC(Cdc20)-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APC(Cdh1)-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2, Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate ApC(Cdc20), whereas Bub2 regulates ApC(Cdh1).

AB - In yeast, anaphase entry depends on Pds1 proteolysis, while chromosome re-duplication in the subsequent S-phase involves degradation of mitotic cyclins such as Clb2, Sequential proteolysis of Pds1 and mitotic cyclins is mediated by the anaphase-promoting complex (APC), Lagging chromosomes or spindle damage are detected by surveillance mechanisms (checkpoints) which block anaphase onset, cytokinesis and DNA re-replication. Until now, the MAD and BUB genes implicated in this regulation were thought to function in a single pathway that blocks APC activity. We show that spindle damage blocks sister chromatid separation solely by inhibiting APC(Cdc20)-dependent Pds1 proteolysis and that this process requires Mad2. Blocking APC(Cdh1)-mediated Clb2 proteolysis and chromosome re-duplication does not require Mad2 but a different protein, Bub2, Our data imply that Mad1, Mad2, Mad3 and Bub1 regulate ApC(Cdc20), whereas Bub2 regulates ApC(Cdh1).

U2 - 10.1093/emboj/18.10.2707

DO - 10.1093/emboj/18.10.2707

M3 - Article

C2 - 10329618

SN - 0261-4189

VL - 18

SP - 2707

EP - 2721

JO - EMBO Journal

JF - EMBO Journal

IS - 10

ER -