NYMC Faculty Publications

The P12 Subunit Choreographs the Regulation and Functions of Two Forms of DNA Polymerase Δ in Mammalian Cells

Author Type(s)

Faculty

DOI

10.3390/genes16020188

Journal Title

Genes

Document Type

Article

Publication Date

2-1-2025

Department

Pathology, Microbiology and Immunology

Second Department

Biochemistry and Molecular Biology

Keywords

cell cycle regulation, DNA damage response, DNA polymerase δ, DNA repair, homology-directed repair, human DNA replication, tumorigenesis

Disciplines

Medicine and Health Sciences

Abstract

There are two forms of DNA polymerase δ in human cells, Pol δ4 and Pol δ3, which differ based on their possession of the p12 subunit. The degradation of p12 has emerged as an important regulatory mechanism that controls the generation of Pol δ3. The underlying importance of this system lies in the altered enzymatic properties of the two forms of Pol δ engendered by the influence of p12. We briefly review how the balance of these two forms is regulated through the degradation of p12. We focus on the roles of Pol δ4, whose cellular functions are less well known. This is significant because recent studies show that this is the form engaged in the homology-dependent repair of double-strand breaks. We consider new horizons for future research into this system and their potential involvement in tumorigenesis.

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