Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila

Marito Araki, Robin P. Wharton, Zhanyun Tang, Hongtao Yu, Maki Asano

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

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 G1 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.

Original languageEnglish (US)
Pages (from-to)6115-6126
Number of pages12
JournalEMBO Journal
Volume22
Issue number22
DOIs
StatePublished - Nov 17 2003

Fingerprint

Origin Recognition Complex
Anaphase-Promoting Complex-Cyclosome
Drosophila
Degradation
Cell Cycle
Cells
Proteolysis
Saccharomycetales
Normal Distribution
G1 Phase
Transcription
Mitosis
Yeast
DNA
Proteins

Keywords

  • APC
  • Cell cycle
  • ORC1
  • Proteolysis
  • Replication

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila. / Araki, Marito; Wharton, Robin P.; Tang, Zhanyun; Yu, Hongtao; Asano, Maki.

In: EMBO Journal, Vol. 22, No. 22, 17.11.2003, p. 6115-6126.

Research output: Contribution to journalArticle

Araki, Marito ; Wharton, Robin P. ; Tang, Zhanyun ; Yu, Hongtao ; Asano, Maki. / Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila. In: EMBO Journal. 2003 ; Vol. 22, No. 22. pp. 6115-6126.
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