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Question 16 0.5 pts Identify the correct sequence of events proposed by the double-stranded break model of homologous recombi

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The correct sequence is 3,1,2,4

|||.Generation of single stranded DNA segments

|.Strand invasion and D loop formation

||.DNA gap repair synthesis

|V.Resolution

Explanation:

Ionizing radiation, chemotherapeutic agents like doxorubicin , oxidative free radicals causes double stranded DNA breaks that are lethal to the cell.

They are repaired by one of the two systems.

  • Nonhomologous end joining- It is error prone and mutagenic. It occurs at any phase of cell cycle.
  • Homeologous recombination- It uses the enzymes that normally perform genetic recombination between homologous chromosomes during meiosis. It is much less error prone,the lost DNA is replaced using homologous DNA as template.It occurs during late S and g2 phase of cell cycle. Initially there is pathway selection.

Steps:

  • The next step is Resection by the MRN complex and DNA2 creates 3′ ssDNA overhangs, which are coated by the Replication protein A (RPA) . In homologous recombination, RPA is displaced by RAD51.
  • RAD51 filament formation is regulated by the positive RAD51 regulators, BRCA etc. (Mutations to the proteins BRCA increases the risk of developing breast and ovarian cancer.)
  • The next step is strand invasion and is regulated by the RAD51 and RAD54.RAD51-mediated D loops are negatively regulated by RTEL.
  • The DNA polymerases enzymes then copies the missing sites from the homologous template.
  • Synthesis-dependent strand annealing occurs and this causes the D loop to be displaced, and the DNA is resolved into a noncrossover product.
  • Then, hetero duplex extension occurs. Following that, there is dissolution or resolution.
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