biostudies-literatureMayle RFoundation for the NIH (FNIH)NIGMS NIH HHSe2517556122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12452832biostudies-literatureUnknown122(37)Replication of cellular chromosomes requires a primase to generate short RNA primers to initiate genomic replication. While bacterial and archaeal primase generate short RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA polymerase (Pol) subunits that function together to form a >20 base hybrid RNA-DNA primer. Interestingly, the DNA Pol1 subunit of Polα lacks a 3'-5' proofreading exonuclease, contrary to the high-fidelity normally associated with DNA replication. However, Polδ and Polε synthesize the majority of the eukaryotic genome, and both contain 3'-5' exonuclease activity for high fidelity. Nonetheless, even the small amount of DNA produced by Pol1 in each of the many RNA/DNA primers during chromosome replication adds up to tens of millions of nucleoProceedings of the National Academy of Sciences of the United States of AmericaDNA polymerase α-primase can function as a translesion DNA polymerase.PMC12452832R35 GM148159GM149862R01 GM149862Mayle RO'Donnell MEGeorgescu RfalseDNA polymerase α-primase can function as a translesion DNA polymerase.Replication of cellular chromosomes requires a primase to generate short RNA primers to initiate genomic replication. While bacterial and archaeal primase generate short RNA primers, the eukaryotic primase, Polα-primase, contains both RNA primase and DNA polymerase (Pol) subunits that function together to form a >20 base hybrid RNA-DNA primer. Interestingly, the DNA Pol1 subunit of Polα lacks a 3'-5' proofreading exonuclease, contrary to the high-fidelity normally associated with DNA replication. However, Polδ and Polε synthesize the majority of the eukaryotic genome, and both contain 3'-5' exonuclease activity for high fidelity. Nonetheless, even the small amount of DNA produced by Pol1 in each of the many RNA/DNA primers during chromosome replication adds up to tens of millions of nucleo2025-01-01T00:00:00Z2025 Sep2026-06-03T19:13:17.688Z2026-05-30T03:06:33.397ZS-EPMC124528324092887910.1073/pnas.2517556122