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Cell Biochem Biophys. 2000;33(2):175-80.

How do drug-induced topoisomerase I-DNA lesions signal to the molecular interaction network that regulates cell cycle checkpoints, DNA replication, and DNA repair?

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Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA.


Recent results suggest that potentially lethal DNA lesions may result when replication forks encounter trapped topoisomerase-DNA complexes or some other types of DNA damage. Such events produce what are called replication-encounter lesions. These lesions have the characteristic that they may allow single stranded DNA-associated replication protein A (RPA) to become juxtaposed to dsDNA end-associated DNA-protein kinase. Our results suggest that DNA-protein kinases may then hyperphosphorylate the RPA2 subunit. We discuss a possible pathway by which hyperphosphorylation of RPA2 could lead to the release of active p53. This could constitute a pathway for signaling the presence of replication-encounter lesions to the p53-dependent cell cycle arrest and/or apoptosis initiator systems.

[Indexed for MEDLINE]

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