p12 isoform-2 is a regulatory subunit of human DNA polymerase delta and is dysregulated in various cancers

Abstract

Dysregulation of human DNA polymerase delta (Polδ) subunits is associated with genome instability and pathological disorders. Genome databases suggest the expression of several spliced variants of subunits which may alter Polδ function. Here, we analyzed the protein-encoding variants of the Polδ subunit p12 and their association with cancer. p12 isoform-2 (p12*) encodes a 79 aa protein with a C-terminal tail distinct from the previously characterized p12. Like p12, p12* dimerizes and interacts with p125 and p50 subunits and is thus an integral component of Polδ. Further, we observed dysregulated p12* expression in low-grade glioma, renal, thyroid, and pancreatic carcinomas. This study identifies a previously unrecognized Polδ complex and highlights a possible regulatory role of p12 variants in cellular phenotypes.