# Mouse PrimPol Outperforms Its Human Counterpart as a Robust DNA Primase

## TL;DR

Mouse PrimPol is more effective than human PrimPol in starting DNA synthesis, due to structural differences that enhance its primase activity.

## Contribution

The study reveals structural and functional differences between mouse and human PrimPol that explain the superior primase activity in mice.

## Key findings

- MmPrimPol has a more powerful primase activity than human PrimPol.
- The shorter linker in MmPrimPol promotes a primase-ready configuration.
- MmPrimPol forms primers more efficiently but has limited DNA polymerization on existing primers.

## Abstract

The human PrimPol counteracts DNA replication stress by repriming DNA synthesis when fork progression is hindered by UV light or hydroxyurea treatment, or by encountering complex DNA structures, such as G-quadruplexes, R-loops, or interstrand crosslinks. The Mus musculus PrimPol (MmPrimPol) shares a high degree of amino acid similarity with its human ortholog; however, as shown here, MmPrimPol exhibits a more powerful primase activity compared to the human enzyme. Such a robust primase activity relies on an enhanced ability to bind the 5′ site nucleotide, and consequently to form initial dimers and further mature primers. Additionally, a shorter linker between the AEP core and the Zn finger domain (ZnFD) in the murine homolog likely promotes a constitutive closing of these domains into a primase-ready configuration. Consequently, a reinforced close configuration of the ZnFD would explain why MmPrimPol has a more robust primase, but a very limited DNA polymerization on an existing primer.