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Sister chromatid separation and chromosome re‐duplication are regulated by different mechanisms in response to spindle damage
Author(s) -
Alexandru Gabriela,
Zachariae Wolfgang,
Schleiffer Alexander,
Nasmyth Kim
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.10.2707
Subject(s) - biology , sister chromatids , gene duplication , chromatid , genetics , chromosome , sister chromatid exchange , gene , dna
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 .