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Regulation of Human DNA Primase-Polymerase PrimPol

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Abstract

Transmission of genetic information depends on successful completion of DNA replication. Genomic DNA is subjected to damage on a daily basis. DNA lesions create obstacles for DNA polymerases and can lead to the replication blockage, formation of DNA breaks, cell cycle arrest, and apoptosis. Cells have evolutionary adapted to DNA damage by developing mechanisms allowing elimination of lesions prior to DNA replication (DNA repair) and helping to bypass lesions during DNA synthesis (DNA damage tolerance). The second group of mechanisms includes the restart of DNA synthesis at the sites of DNA damage by DNA primase-polymerase PrimPol. Human PrimPol was described in 2013. The properties and functions of this enzyme have been extensively studied in recent years, but very little is known about the regulation of PrimPol and association between the enzyme dysfunction and diseases. In this review, we described the mechanisms of human PrimPol regulation in the context of DNA replication, discussed in detail interactions of PrimPol with other proteins, and proposed possible pathways for the regulation of human PrimPol activity. The article also addresses the association of PrimPol dysfunction with human diseases.

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Acknowledgments

The authors are grateful to Yu. I. Pavlov and A. G. Baranovskiy for valuable discussions and advice.

Funding

This work was supported by the Russian Science Foundation (grant no. 22-24-20150 to E.O.B).

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Authors and Affiliations

  1. Kurchatov Institute National Research Centre, 123182, Moscow, Russia

    Elizaveta O. Boldinova & Alena V. Makarova

  2. Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    Elizaveta O. Boldinova & Alena V. Makarova

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  1. Elizaveta O. Boldinova
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E.O.B. figure preparation, writing the draft of the paper; A.V.M. draft correction.

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Correspondence to Elizaveta O. Boldinova.

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Boldinova, E.O., Makarova, A.V. Regulation of Human DNA Primase-Polymerase PrimPol. Biochemistry Moscow 88, 1139–1155 (2023). https://doi.org/10.1134/S0006297923080084

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