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DNA Damage/Repair Management

DNA Damage/Repair Management

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ChemDiv offers high throughput screening (HTS) service

DNA Damage/Repair Management research platform

  • 173 assays, 8 groups of targets based on the DNA damage/repair pathway are available

DNA Damage/Repair pathways: base excision repair (BER), direct reversal repair (DRR), DNA damage signaling (DDS), homologous recombination repair (HRR), mismatch repair (MMR), nonhomologous end-joining (NHEJ), nucleotide excision repair (NER), translesion synthesis (TLS)

  • High content screening platform and 3 lead characterization methods: ELISA, flow cytometry, western blotting

  • Track record of 25+ years’ experience, expertise in all major therapeutic areas

  • Full discovery support of your projects

CADD, synthetic and medicinal chemistry, preclinical biology, animal studies, CMC and formulation

  • Screening of up to 1.6M compounds

Cherry-pickable collection

  • Support for compound selection

Custom selection and screening set preparation from 1.6M stock available compounds

More details on prices, time, or research specificity - please contact chemdiv@chemdiv.com


The crucial goal for targeting DNA damage/repair proteins is to diminish the survivability of the cancer cells. For instance, DNA-PKcs central role in the repair of double-stranded breaks in DNA makes this protein a perfect target for small molecule studies. Another example of such regulation is ATM and ATR catalytic activity inhibition by caffeine, which sensitizes tumor cells to ionizing radiation.

High-throughput screening systems allow the study of different aspects of DNA damage and repair management in cells. ChemDiv offers following assay platform:

High content (HC):

  • The cellular model is exposed to the stimulus of interest

  • The added fluorescent compounds interact with the histone marking damaged fragment of DNA

  • Magnitude of the fluorescence is processed and analyzed by complex algorithms automatically

  • The signal from the images of cells is recorded from all the wells of 384-well microplate

Figure 1. Schematic algorithm of the high content screening. The necessity of a stimulus of interest is to trigger DNA damage response pathways in cells.


ChemDiv also provides methods for the lead characterization, such as ELISA, flow cytometry and western blotting:

ELISA

  • Numerous markers produced by cell based on how DNA was damaged serve as antigens for the studies

  • The antigens are bound to the wells of a microplate

  • Specific to the antigen antibodies, then reporter antibodies and coloring agents are added to tag the molecule of interest

  • Change in color allows to indirectly measure the amount of damaged DNA

Flow cytometry

  • A suspended sample of dye-loaded cells is arranged in a single line to pass through laser beam one by one

  • Signal from passing cells is registered to count and characterize them

  • Histone marking DNA damage is tagged by fluorescently labeled antibody

  • Approximately 10000 cells can be analyzed in less than one minute

Western blotting

  • Proteins are separated via the gel electrophoresis based on their molecular weight

  • Polyvinylidene fluoride (PDVF) membrane produces a band for each of the proteins

  • Incubation with specific antibodies leads to the localization of the protein of interest

  • The thickness of the remaining band directly depends on the amount of protein present


List of targets:

  • Base excision repair (BER)

  • Direct reversal repair (DRR)

  • DNA damage signaling (DDS)

  • Homologous recombination repair (HRR)

  • Mismatch repair (MMR)

  • Nonhomologous end-joining (NHEJ)

  • Nucleotide excision repair (NER)

  • Translesion synthesis (TLS)

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