Regulacion Del Ciclo Celular De La Replicacion De Dna

Cell Cycle Regulation of DNA Replication
R. A. Sclafani and T. M. Holzen
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine,
Aurora, Colorado 80045;email: robert.sclafani@uchsc.edu, Teresa.Holzen@UCHSC.edu
Abstract
Eukaryotic DNA replication is regulated to ensure all chromosomes replicate once and only once
per cell cycle. Replication begins atmany origins scattered along each chromosome. Except for
budding yeast, origins are not defined DNA sequences and probably are inherited by epigenetic
mechanisms. Initiation at origins occursthroughout the S phase according to a temporal program
that is important in regulating gene expression during development. Most replication proteins are
conserved in evolution in eukaryotes and archaea,but not in bacteria. However, the mechanism of
initiation is conserved and consists of origin recognition, assembly of pre-replication (pre-RC)
initiative complexes, helicase activation, andreplisome loading. Cell cycle regulation by protein
phosphorylation ensures that pre-RC assembly can only occur in G1 phase, whereas helicase
activation and loading can only occur in S phase. Checkpointregulation maintains high fidelity by
stabilizing replication forks and preventing cell cycle progression during replication stress or damage.

Keywords
origins; kinase; helicase; checkpoint;replisome; replicons

INTRODUCTION
Le rêve d’une bactérie doit devenir deux bactéries (The dream of a bacterium is to
become two bacteria)
François Jacob, 1965
As François Jacob said poeticallyover 40 years ago, it is a cell’s “dream” to become two cells
with identical copies of the genome. Thus the replication of the genome must be an exact
process. Errors that result in underreplicationor overeplication of the genome in any cell cycle
have disastrous consequences and can produce a large array of human genetic diseases,
including cancer, birth defects, and many developmental...