DNA Damage Repair (DDR) Screening Platform
DNA Damage Repair (DDR) is a general term for the mechanism by which cells recognize and repair DNA damage. In cells, both endogenous normal metabolic activity and exogenous factors can cause DNA damage. DNA damage can have a variety of consequences, such as affecting the normal transcription of genes, causing instability in the genetic material, and the viability of offspring cells.DNA damage, if not repaired in a timely manner, may eventually lead to the development of tumors and cancers.
There are many types of DNA damage, such as DNA single-strand damage, double-strand damage, or base mismatch. The repair signaling pathways and key proteins involved vary greatly depending on the type of injury.Given the close relationship between DDR and carcinogenesis, DDR-related targets and experimental methods are not only a hot topic for biopharmaceutical companies, but also a platform for LeadQuest Biotech to vigorously develop.
DDR Pathways and Targets
For different DDR pathways and targets, LeadQuest Biotech has prepared different methods from protein, enzyme to cytology for customers to choose from.
List of Testing Method
• Biochemical methods for polymerase, helicase, nuclease and reverse transcriptase activities
• Cell proliferation, apoptosis and cell cycle detection
• Compound toxicity testing
• DDR path reporting method
• DNA damage detection methods
1.Protein Purification and Validation
LeadQuest Biotech’s state-of-the-art equipment and extensive experience in purifying and validating DDR-related proteins. Prokaryotic and eukaryotic system are both available.
2.WRN Related Target
Werner’s syndrome protein (WRN), which is a major member of the RecQ DNA helicase family. WRN proteins are widely involved in the replication, transcription, recombination, and repair of nucleic acids. Mutations in WRN contribute to the development of Werner syndrome and are also thought to be associated with tumors and a variety of other diseases.
LeadQuest Biotech use enzymatic and cytological methods to detect the corresponding activity of the RecQ family member proteins, such as Unwinding Assay, ADP-Glo Assay, Cell Proliferation, etc., for the different functional domains of the RecQ family member proteins.
3.PARP/PARG Related Target
Poly (ADP-ribose) polymerase 1 (PARP1) is an important member of the polyADP-ribosyltransferase family. As a pioneer factor in DNA damage repair, PARP1 has been reported to be recruited to the site of damage within a very short time after the occurrence of the lesion, and the base excision repair (BER) is regulated by polyADP-ribosylated XRCC1. In addition, it has also been reported to be involved in the regulation of DNA double-strand break repair (DSBR) and nucleotide excision repair (NER). PARP1 is a star molecule in the field of tumor therapy, and PARP inhibitors (PARPi) have been widely used in the treatment of a variety of tumors, especially in the clinical treatment of breast cancer, ovarian cancer and other tumors with BRCA1/2 deletion.
In contrast to poly-ADP-ribose, the hydrolysis of poly-ADP-ribose also plays an important role in the process of DNA damage repair. Poly (ADP-ribose) glycohydrolase (PARG) is one of the major members of polyADP-ribohydrolase.
LeadQuest Biotech has also designed and validated a series of biochemical synthetical cytology method for the PARP family and PARG to facilitate compound screening.
4.POLQ Related Target
The DNA polymerase theta is an enzyme encoded by the POLQ gene in humans. This polymerase plays a key role in one of three major double-strand break repair pathways: Theta-mediated end joining (TMEJ). Most double-strand breaks are repaired by non-homologous end joining (NHEJ) or homologous recombination repair (HDR). However, in some cases, defects in NHEJ and HR make TMEJ the only way to repair DNA double-strand breaks. Thus, POLQ is a synthetically lethal novel target in HR or NHEJ deficient cells.
LeadQuest Biotech provide compound screens for POLQ targets, including the industry-leading TMEJ Reporter Assay.
5.p53 Related Target
p53 is a tumor suppressor protein and transcription factor that regulates cell division, preventing cells with DNA mutations or damage from dividing and signaling apoptosis to these cells through transcriptional regulation, thereby preventing tumor formation.
6.PRMT5-MAT2A Related Target
PRMT (protein arginine methyltransferase) is able to methylate a variety of proteins and plays an important role in biological processes such as gene expression, splicing, and DNA damage repair. MTAP (methylthioadenosine phosphorylase) often co-deletion with the common tumor suppressor gene CDKN2A in the body, and the proportion of this codeletion in tumors can reach 9%~15%. Synthetic lethal effects of PRMT5 in MTAP-deficient tumors. In addition, MTAP-deficient cancer cells have also been shown to be sensitive to methionine adenosyltransferase 2A (MAT2A). Therefore, PRMT5 inhibitors and MAT2A inhibitors are expected to become a new generation of targeted drugs for the treatment of MTAP-deficient tumors.
Cell Panel Screening
LeadQuest Biotech has been aggressively expanding the company’s cell line library. The company has nearly 600 human cancer cell lines. At the same time, we are also actively constructing engineered cell lines with knockout, knockoff and overexpression of key DDR proteins to meet the needs of pharmaceutical companies for the screening of cell panels of different cancer types, drug-susceptible strains and drug-resistant strains.