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Degradation of origin recognition complex large subunit by the anaphase‐promoting complex in Drosophila
Author(s) -
Araki Marito,
Wharton Robin P,
Tang Zhanyun,
Yu Hongtao,
Asano Maki
Publication year - 2003
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/cdg573
Subject(s) - library science , biology , computer science
The initiation of DNA synthesis is thought to occur at sites bound by a heteromeric origin recognition complex (ORC). Previously, we have shown that in Drosophila , the level of the large subunit, ORC1, is modulated during cell cycle progression and that changes in ORC1 concentration alter origin utilization during development. Here, we investigate the mechanisms underlying cell cycle‐dependent degradation of ORC1. We show that signals in the non‐conserved N‐terminal domain of ORC1 mediate its degradation upon exit from mitosis and in G 1 phase by the anaphase‐promoting complex (APC) in vivo . Degradation appears to be the result of direct action of the APC, as the N‐terminal domain is ubiquitylated by purified APC in vitro . This regulated proteolysis is potent, sufficient to generate a normal temporal distribution of protein even when transcription of ORC1 is driven by strong constitutive promoters. These observations suggest that in Drosophila , ORC1 regulates origin utilization much as does Cdc6 in budding yeast.