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 -