PUBLICATION

Zebrafish Polymerase Theta and human Polymerase Theta: Orthologues with homologous function

Authors
Thomas, C., Green, S., Kimball, L., Schmidtke, I.R., Rothwell, L., Griffin, M., Par, I., Schobel, S., Palacio, Y., Towle-Weicksel, J.B., Weicksel, S.E.
ID
ZDB-PUB-250430-2
Date
2025
Source
PLoS One   20: e0321886e0321886 (Journal)
Registered Authors
Keywords
none
MeSH Terms
none
PubMed
40299938 Full text @ PLoS One
Abstract
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 different divalent metals, microhomology-mediated end joining, and translesion synthesis. These results will support future studies looking to gain insight into Pol θ function on the basis of evolutionarily conserved features.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping