Nvp63 and nvPIWIL1 Suppress Retrotransposon Activation in the Sea Anemone Nematostella vectensis

The transcription factors p63 and
p73 have high similarity to the
tumor suppressor protein p53. While the importance of p53 in DNA damage
control is established, the functions of p63 or p73 remain elusive.
Here, we analyzed nvp63, the cnidarian homologue of p63, that is expressed
in the mesenteries of the starlet sea anemone Nematostella
vectensis and that is activated in response to DNA
damage. We used ultraviolet light (UV) to induce DNA damage and determined
the chromatin-bound proteome with quantitative, bottom-up proteomics.
We found that genotoxic stress or nvp63 knockdown recruited the protein
nvPIWIL1, a homologue of the piRNA-binding PIWI protein family. Knockdown
nvPIWIL1 increased protein expression from open reading frames (ORFs)
that overlap with class I and II transposable element DNA sequences
in the genome of N. vectensis. UV irradiation
induced apoptosis, and apoptosis was reduced
in the absence of nvp63 but increased with the loss of nvPIWIL1. Loss
of nvp63 increased the presence of class I LTR and non-LTR retrotransposon
but not of class II DNA transposon-associated protein products. These
results suggest that an evolutionary early function of nvp63 might
be to control genome stability in response to activation of transposable
elements, which induce DNA damage during reintegration in the genome.