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DNA Polymerase Theta (POLQ)

POLQ, or DNA polymerase theta, is an enzyme that plays a significant role in the DNA damage response (DDR), particularly in the repair of double-strand breaks (DSBs) through a process known as theta-mediated end-joining (TMEJ), which is also referred to as microhomology-mediated end-joining (MMEJ). It has emerged as a promising synthetic lethality target, especially in the context of cancers with deficiencies in homologous recombination (HR), such as those associated with mutations in BRCA1/2.

Interest in POLQ as a target for cancer therapy is driven by its potential to exploit the synthetic lethal interaction with HR-deficient cancers. Inhibition of POLQ in these cancer cells can lead to genomic instability and cell death, which forms the basis of its therapeutic strategy.

ICE Bioscience has constructed a cascade from in vitro to in vivo, comprising protein production, biochemical assays, cell line construction, cellular assays, and animal modeling. Our POLQ screening cascade empowers the mechanistic study of POLQ and ensures an efficient and comprehensive screening process for POLQ inhibitors, thereby accelerating the discovery of new drugs.


Assay List

▶ POLQ Protein Production

▶ Biochemical Assays:

1.  POLQ ADP-Glo Assay (N-terminal)

2.  POLQ Picogreen Assay (C-terminal)

3.  POLQ TR-FRET Assay (C-terminal)

4.  Selectivity Assay (Polα, Polγ, Polη, Polν, DNA binding)

▶ Cellular Assays:

1.  Cell Proliferation Assay

2.  NHEJ and HR Reporter Assays

3.  Clonogenic Assay

4.  γH2AX IFA and WB Assays

5.  Drug Sensitive/Resistant Cell Line Generation

6.  Cell Panel Screening

7.  Western Blot for POLQ Degradation Detection

▶ In Vivo Efficacy Studies



 Additional Resources 

APPLICATION NOTE: 

Comprehensive POLQ Screening for Targeted Drug Discovery


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