DNA polymerase kappa supports genome repair in cultured neurons
In mouse and human neurons, depleting POLK reduced repair-associated DNA synthesis and induced senescence-like stress, while augmenting POLK lowered DNA damage markers.
bioRxiv
In primary mouse cortical neurons and human induced pluripotent stem cell-derived forebrain neurons, researchers assessed the consequences of altering DNA polymerase kappa (POLK). Partial POLK depletion reduced EdU incorporation, diminished neuronal arbor complexity, enlarged nuclei, and triggered a multidimensional senescence-like stress phenotype with increased senescence-associated beta-galactosidase and p21. In wild-type neurons, POLK depletion increased 6E10 immunoreactivity and remodeled APP, lipid, and lysosomal pathways. In APOE e4/e4 neurons, POLK depletion increased cytoplasmic double-stranded DNA and phospho-tau. Conversely, augmenting POLK increased EdU incorporation and reduced markers of DNA damage, including 53BP1 and gamma-H2AX, along with p38 MAPK, cytoplasmic double-stranded DNA, 6E10 immunoreactivity, and phospho-tau.
Why it matters
The findings suggest POLK plays a role in repair-associated DNA synthesis in mature neurons, linking its availability to neuronal stress resilience during aging and neurodegenerative conditions.
Caveats
The experiments were conducted in vitro using cultured mouse and human neurons rather than intact brain tissue, and the study is a preprint that has not undergone peer review.
The paper
DNA polymerase kappa supports repair-associated DNA synthesis and neuronal genome resilience
Goyal G, Palanisamy P, Paul A et al.
bioRxiv · 4 Oct 2026 · Preprint, not peer-reviewed