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Nascent ssDNA IF assay

Nascent ssDNA by BrdU staining download

Nascent ssDNA by native BrdU staining (Jami, 2014)

Plate 300,000 U2OS cells in 6-well format (on either 15CIR or 22CIR coverslips) the afternoon before.

Cell Treatment:

  1. Pulse cells for 10 minutes with 10uM BrdU.
  2. Add HU to 3mM and ATRi to 5uM for 4h.
  3. After 4h, place cells on ice and proceed with immunostaining.

Immunostaining Procedure:

  1. Rinse cells once in PBS. Aspirate.
  2. Add .5-1mL Triton X solution, 10 min on ice.
  3. Wash 3x 1ml PBS carefully.
  4. Add 1-2mL paraformaldehyde/sucrose fixative, 10 minutes, room temp.
  5. Rinse 3x 1ml PBS. Cells can be stored in cold room/fridge at this step, leave in PBS.
  6. Block with 5% BSA/PBS, 15 min, room temp.
  7. Secure parafilm on lid of 6-well plate (if in coverslip format).
  8. Spin primary antibodies at 16,100g for 5 minutes to remove debris. (Not necessary)
  9. Add 35uL (50 for 22CIR) primary antibody as a drop on parafilm. Place coverslip face down on parafilm. 1h at 37deg.
  10. Rinse 3x 1ml PBS.
  11. Repeat 8-10 for secondary antibody. 30 minutes at room temp (dark).
  12. Thaw Prolong Gold with DAPI solution. Dab a small droplet using 1mL pipet tip onto slides. (5-10ul for 15CIR)
  13. Aspirate PBS from back of coverslip, aspirate all large water droplets from coverslip surface. Mount, remove bubbles and excess mounting solution. Allow slides to dry for a few hours or overnight before viewing.
    Note: if doing 96-well format, add 35-50uL antibody solution to each well. Other steps should be similar.

Solutions:

Fixative (3% paraformaldehyde/2% sucrose): Dissolve 15g paraformaldehyde in 250mL water. Incubate 20min in 65-deg bath. Add 3 drops 10.0N NaOH. Incubate 5-10 minutes longer at 65deg. Add 50mL 10x PBS, 10g sucrose, dissolve and bring to 500mL. Filter, aliquot, and store at -20deg. Do not freeze-thaw, use a fresh tube each time.
Triton X-100 solution: (for 50mL) 0.5% Triton X-100 (1.25mL 20% stock), 20mM HEPES, pH 7.4 (2mL .5M stock), 50mM NaCl (.5mL 5M stock), 3mM MgCl2 (.15mL 1M stock), 300mM sucrose (5.134g). Dissolve, filter, store 4deg. This solution only lasts a few weeks.

Antibodies:

  1. Mouse anti-BrdU (BD, use 1:50 in 3% BSA/PBS)
  2. Goat anti-mouse Alexa 488 (Invitrogen, use 1:500 in 3% BSA/PBS)