biostudies-literatureThomas CRhode Island IDeA Networks of Biomedical Research ExcellenceNational Institute of General Medical SciencesNIGMS NIH HHSe0321886https://www.ebi.ac.uk/biostudies/studies/S-EPMC12040184biostudies-literatureUnknown20(4)DNA Polymerase Theta (Pol θ) is a conserved an A-family polymerase that plays an essential role in repairing double strand breaks, through micro-homology end joining, and bypassing DNA lesions, through translesion synthesis, to protect genome integrity. Despite its essential role in DNA repair, Pol θ is inherently error-prone. Recently, key loop regions were identified to play an important role in key functions of Pol θ. Here we present a comparative structure-function study of the polymerase domain of zebrafish and human Pol θ. We show that these two proteins share a large amount of sequence and structural homology. Using a classical biochemical approach we observe that zebrafish Pol θ displays behavior characteristic of human Pol θ, including DNA template extension in the presence of difPloS oneZebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function.PMC12040184P20GM103430R15GM144903-01P20 GM103430R15 GM144903Towle-Weicksel JBThomas CGreen SKimball LSchmidtke IRWeicksel SEGriffin MPalacio YRothwell LPar ISchobel SfalseZebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function.DNA Polymerase Theta (Pol θ) is a conserved an A-family polymerase that plays an essential role in repairing double strand breaks, through micro-homology end joining, and bypassing DNA lesions, through translesion synthesis, to protect genome integrity. Despite its essential role in DNA repair, Pol θ is inherently error-prone. Recently, key loop regions were identified to play an important role in key functions of Pol θ. Here we present a comparative structure-function study of the polymerase domain of zebrafish and human Pol θ. We show that these two proteins share a large amount of sequence and structural homology. Using a classical biochemical approach we observe that zebrafish Pol θ displays behavior characteristic of human Pol θ, including DNA template extension in the presence of dif2025-01-01T00:00:00Z20252026-06-01T10:17:42.176Z2025-07-10T03:09:11.465ZS-EPMC120401844029993810.1371/journal.pone.0321886