Cell cycle control of the initiation of genome replication

Hruce Stillman, James Chong, Chnn Liang, Hai Rao, Michael Weinreich, Lee Zon

Research output: Contribution to journalArticlepeer-review


The initiation of DNA replication in eukaryotes is determined by a large multi-protein complex (hat forms a pre-replicative assembly at the origin of DNA replication prior to the initiation in the S phase of the cell cycle. The Origin Recognition Complex (ORC) is the focal point of the1 assembly and other proteins, such as Cdcop and the Mini Chromosome Maintenance (Mem) proteins interact directly or indirectly with ORC to form a competent complex. ORC' is physically associated with the chromosomes during the entire cell cycle but thai the Mem proteins arc cell cycle regulated in their association, being displaced from the chrornatin during S phase and loaded during M phase. We have identified (,'D("6 mutants that allo\v continual initiation of D,\A replication, even during nocodozole arrested M phase. In these cdcfj mutants, the Mcni proteins remain bound to the chromatin. during and after the 1).\A has replicated. Thus, the mutant Cdc6p causes these chromosomes to be permanently competent for the initiation of DNA replication. In other studies, we have uncovered a role for the proteins that control the separation of sister chromât id s during a nap hase in the regulation of the initiation of DNA replication. Control of UNA replication by the anaphase promoting complex (APC) appears to be mediated by Pdslp and the Dbf-tp subunit of the Cdc7p protein kinase. We suggest from genetic studies that there are two parallel pathways that activate the competent pre-replication complex and ensure one round of replication per cell cycle. These same pa! h way h also control progrès .sinn through mitosis.

Original languageEnglish (US)
Pages (from-to)A1014
JournalFASEB Journal
Issue number9
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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