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Research

Repetitive protein domains

Repetitive protein domains: Important regulatory sequences or byproducts of polynucleotide expansion

Eukaryotic genomes are littered with repetitive DNA sequences. The repetitive nature of these sequences makes them unstable to processes such as replication and recombination resulting in a high frequency of expansion/contraction, recombination and DNA damage. As such, repetitive DNA elements are associated with a number of genetic disorders including Huntington's disease, fragile X syndrome, and a number of neuromuscular ataxias (See the Mirkin and Freudenreich labs at Tufts). However, more than 50% of eukaryotic proteins are also predicted to have repetitive protein sequences (derived from repetitive DNA elements), many of which are evolutionarily concerned. This suggests these repetitive regions do more than just cause disease and may also play functional regulatory roles in cells. One well-studied example is the repetitive C-terminal domain (CTD) of RNA polymerase II (RNAPII). This heptapeptide sequence (YSPTSPS) is tandemly repeated between 26 and 52 times in all eukaryotes from yeast to humans and functions as a scaffold for the association of numerous transcription-associated factors. We are interested in understanding how these repetitive protein sequences evolved, how the number of repeats is regulated, and what functions they are playing in the cell.

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