DNA Sliding Clamps as Therapeutic Targets

Chromosomal DNA replication is achieved by an assembly of multi-protein complexes at the replication fork. DNA sliding clamps play an important role in this assembly and are essential for cell viability. Inhibitors of bacterial (β-clamp) and eukaryal DNA clamps, proliferating cell nuclear antigen (P...

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Bibliographic Details
Published in:Frontiers in molecular biosciences 2018-10, Vol.5, p.87-87
Main Authors: Altieri, Amanda S, Kelman, Zvi
Format: Article
Language:English
Subjects:
DNA clamp
DNA sliding clamp
Molecular Biosciences
PCNA
proliferating cell nuclear antigen
therapeutic
β-clamp
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Summary:Chromosomal DNA replication is achieved by an assembly of multi-protein complexes at the replication fork. DNA sliding clamps play an important role in this assembly and are essential for cell viability. Inhibitors of bacterial (β-clamp) and eukaryal DNA clamps, proliferating cell nuclear antigen (PCNA), have been explored for use as antibacterial and anti-cancer drugs, respectively. Inhibitors for bacterial β-clamps include modified peptides, small molecule inhibitors, natural products, and modified non-steroidal anti-inflammatory drugs. Targeting eukaryotic PCNA sliding clamp in its role in replication can be complicated by undesired effects on healthy cells. Some success has been seen in the design of peptide inhibitors, however, other research has focused on targeting PCNA molecules that are modified in diseased states. These inhibitors that are targeted to PCNA involved in DNA repair can sensitize cancer cells to existing anti-cancer therapeutics, and a DNA aptamer has also been shown to inhibit PCNA. In this review, studies in the use of both bacterial and eukaryotic sliding clamps as therapeutic targets are summarized.
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2018.00087