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Comparative analysis of the molecular mechanisms controlling the initiation of chromosomal DNA replication in yeast and in mammalian cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
14587 1232 2012 26 PDF Available
Title
Comparative analysis of the molecular mechanisms controlling the initiation of chromosomal DNA replication in yeast and in mammalian cells
Abstract

In eukaryotes DNA replication takes place in the S phase of the cell cycle. It initiates from hundreds to thousands of replication origins in a coordinated manner, in order to efficiently duplicate the genome. The sequence of events leading to the onset of DNA replication is conventionally divided in two interdependent processes: licensing—a process during which replication origins acquire replication competence but are kept inactive— and firing—a process during which licensed origins are activated but not re-licensed.In this review we investigate the evolutionary conservation of the molecular machinery orchestrating DNA replication initiation both in yeast and in mammalian cells, highlighting a remarkable conservation of the general architecture of this central biological mechanism. Many steps are conserved down to molecular details and are performed by orthologous proteins with high sequence conservation, while differences in molecular structure of the performing proteins and their interactions are apparent in other steps.Tight regulation of initiation of DNA replication is achieved through protein phosphorylation, exerted mostly by Cyclin-dependent kinases in order to ensure that each chromosome is fully replicated once, and only once, during each cycle, and to avoid the formation of aberrant DNA structures and incorrect chromosomal duplication, that in mammalian cells are a prerequisite for genome instability and tumorigenesis.We then consider a molecular mathematical model of DNA replication, recently proposed by our group in a collaborative project, as a frame of reference to discuss similarities and differences observed in the regulatory program controlling DNA replication initiation in yeast and in mammalian cells and discuss whether they may be dependent upon different functional constraints. We conclude that a systems biology approach, integrating molecular analysis with modeling and computational investigations, is the best choice to investigate the control of DNA replication in mammalian cells.

Keywords
DNA replication; Cell cycle; Replication origins; Licensing; Firing; pre-Replication Complex; Cyclin-dependent kinase; Yeast; Mammalian cells; Systems biology
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Comparative analysis of the molecular mechanisms controlling the initiation of chromosomal DNA replication in yeast and in mammalian cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biotechnology Advances - Volume 30, Issue 1, January–February 2012, Pages 73–98
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us