Díaz-Talavera, AlbertoMontero-Conde, CristinaLeandro-García, Luis JavierRobledo Batanero, Mercedes2025-01-132025-01-132022-02-03Biomolecules . 2022 Feb 3;12(2):248.https://hdl.handle.net/20.500.12105/26010DNA replication can encounter blocking obstacles, leading to replication stress and genome instability. There are several mechanisms for evading this blockade. One mechanism consists of repriming ahead of the obstacles, creating a new starting point; in humans, PrimPol is responsible for carrying out this task. PrimPol is a primase that operates in both the nucleus and mitochondria. In contrast with conventional primases, PrimPol is a DNA primase able to initiate DNA synthesis de novo using deoxynucleotides, discriminating against ribonucleotides. In vitro, PrimPol can act as a DNA primase, elongating primers that PrimPol itself sythesizes, or as translesion synthesis (TLS) DNA polymerase, elongating pre-existing primers across lesions. However, the lack of evidence for PrimPol polymerase activity in vivo suggests that PrimPol only acts as a DNA primase. Here, we provide a comprehensive review of human PrimPol covering its biochemical properties and structure, in vivo function and regulation, and the processes that take place to fill the gap-containing lesion that PrimPol leaves behind. Finally, we explore the available data on human PrimPol expression in different tissues in physiological conditions and its role in cancer.A.D.-T. is the recipient of a Postdoctoral Research Scientist contract from Centro de Investigacion Biomedica en Red Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII). L.J.L.-G. was supported both by the Banco Santander Foundation - CNIO Fellowship and by "la Caixa" Foundation (ID 100010434), under agreement LCF/BQ/PI20/11760011.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/PrimPolcancergenomic instabilitypolymeraseprimasereplication stressreprimingAttribution-NonCommercial-NoDerivatives 4.0 International35204749122248Biomoleculesopen access