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The Effect of Parp3 Inhibitor Treatment on Activated B cells


DNA repair mechanisms are necessary for preserving the integrity of the genome. However, mutations can sometimes be advantageous. Activated B cells upregulate expression of activation induced deaminase (AID), which is recruited to genes encoding the B cell receptor (BCR) and deaminates cytosines into uracils on single-stranded DNA.

When AID acts on cytosines in switch regions of the heavy chain (IgH) genes, double-stranded breaks (DSBs) can occur in these regions during the process of DNA repair and the IgH locus undergoes a process called class-switch recombination (CSR).

As with DNA damage induced in other parts of the genome, DNA damage repair proteins are recruited to lesions induced by AID. Researchers recently investigated the importance of Parp3, a DNA damage repair protein, by transducing wild-type and Parp3-/- mouse B cells with a retrovirus encoding Flag-tagged Parp3 and a GFP reporter.

Which of the following best explains the results seen in the figure below?

Robert, Isabella, Léa Gaudot, Mélanie Rogier, Vincent Heyer, Aurélia Noll, Françoise Dantzer, and Bernardo Reina-San-Martin. "Parp3 Negatively Regulates Immunoglobulin Class Switch Recombination." PLOS Genetics 11.5 (2015): n. pag. 22 May 2015. Web. 13 Mar. 2016. http://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1005240.


Over-expression of Parp3 does not affect CSR in wild-type B cells or Parp3-/- B cells.


Over-expression of Parp3 reduces CSR in Parp3-/- B cells.


Over-expression of Parp3 reduces CSR in both wild-type and Parp3-/- B cells.


The researchers did not use appropriate controls, so it is unclear whether over-expression of Parp3 has any effect on CSR.