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Initiation of DNA replication in multicellular eukaryotes
Susan A Gerbi1, Zaklina Strezoska, John M Waggener
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University Division of Biology and Medicine, J. W. Wilson Laboratory, 69 Brown Street (Box G-319), Providence, RI 02912, USA. Susan.Gerbi@Brown.edu
Journal of Structural Biology
|December 20, 2002
Summary
DNA replication in eukaryotes begins at specific sites, guided by the origin recognition complex (ORC). Initiation site selection and regulation ensure replication occurs only once per cell cycle, with variations observed in flies during development.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Understanding DNA replication initiation in eukaryotes is crucial.
- Key questions involve the location, determination, and cell-cycle regulation of replication origins.
- The origin recognition complex (ORC) plays a vital role in initiating DNA synthesis.
Purpose of the Study:
- To investigate the precise start sites of DNA replication.
- To explore factors influencing replication initiation site selection.
- To understand the regulation of replication origins for once-per-cell-cycle firing.
Main Methods:
- Comparative analysis of replication initiation in yeast (ARS1) and the fly (Sciara II/9A).
- Examination of origin recognition complex (ORC) binding sites and their relation to DNA synthesis start points.
- Investigation of developmental changes in initiation zones during DNA puff amplification in Sciara.
Main Results:
- Defined replication start sites adjacent to ORC-binding sites were identified in both yeast and Sciara.
- ORC binding preference for DNA sequences exists, but is modulated by other factors.
- Replication initiation zones in Sciara exhibit developmental plasticity, influenced by transcription and chromatin structure.
- Mechanisms for preventing rereplication differ between yeast (pre-RC stabilization) and flies (locus-specific amplification).
Conclusions:
- DNA replication initiation in eukaryotes involves defined start sites influenced by ORC and other factors.
- Replication initiation site selection and regulation are complex processes, varying across organisms and developmental stages.
- Distinct mechanisms govern whole-genome versus locus-specific DNA amplification, highlighting evolutionary adaptations.