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Drug Discov Today. 2001 Aug 1;6(15):786-792.

Targeting the molecular mechanism of DNA replication.

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DNA Biophysics Laboratory, Pasteur Institute, 25 Rue du Dr Roux, 75724 Cedex, Paris, France


Genome stability is crucial for the complete maintenance of the cellular pathways that govern the cell cycle. As a result of irregularities in DNA replication occurring throughout the S phase, key genes that regulate cell cycle pathways are damaged, giving rise to single-base mutations and chromosomal aberrations. Thus, the efficient replication of the genome, which depends on a precise temporal and spatial pattern of activation of origins of replication, is greatly impaired. The approach discussed below aims at monitoring the replication pattern and the kinetics of replication throughout the entire genome of living cells. It could shed light on the mechanisms by which drugs act on DNA replication and, moreover, it might assist the discovery and design of novel drugs that inhibit cell proliferation under pathophysiological conditions.

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