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Helicase Domain of DNA Polymerase Theta (Polθ HLD)
- Target
- Polθ HLD
- Molecular classification
- Enzyme, Helicase, SF2 Helicase, Ski2-like Helicase
01
Overview
The helicase domain of DNA polymerase theta (Polθ) is an N-terminal SF2 helicase domain uniquely found in this polymerase. It is essential for theta-mediated end joining (TMEJ), an alternative DNA double-strand break repair pathway. The HLD acts as a highly processive ssDNA motor, stripping RPA and facilitating microhomology search and annealing. It is a promising therapeutic target in HR-deficient cancers.
- Other names
- POLQ Helicase DomainPolymerase Theta Helicase-like DomainHLD of PolθSF2 Helicase of POLQ
02
Mechanism of action
Inhibition of helicase activity disrupts TMEJ and sensitizes HR-deficient cancer cells
03
Biological functions
RPA removal from ssDNARAD51 filament disassemblyMicrohomology-mediated annealingATP hydrolysisDNA repairssDNA bindingDNA bridging
04
Disease associations
CancerGenomic instabilityDNA repair deficiency
05
Safety considerations
Potential off-target effects on other helicasesDevelopment of resistance through alternative repair pathways
06
Biomarkers
POLQ expression levelsHRD statusTMEJ signature mutations
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