Regulation of human dna primase-polymerase primpol

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 replication blockage, DNA break formation, cell cycle disruption and apoptosis. Cells have adapted to DNA damage evolving mechanisms allowing to eliminate lesions prior to DNA replication (DNA repair) and mechanisms which help to bypass lesions during DNA synthesis (DNA damage tolerance). The second group of pathways includes the mechanism of DNA synthesis restart at the damaged sites by DNA primase-polymerase PrimPol. Human PrimPol was first described in 2013. The properties and functions of PrimPol have been extensively studied in recent years, but very little is known about the regulation of PrimPol and the association of the enzyme dysfunction with diseases. The present review is devoted to an analysis of the mechanisms of human PrimPol regulation in the context of DNA replication. The interaction of PrimPol with other proteins is discussed in detail and an attempt is made to compile a possible pathway for the regulation of human PrimPol activity. The paper also addresses the relationship of PrimPol dysfunction with human diseases.