Expansions of trinucleotide repeats are associated with genetic disorders such as Friedreich's ataxia. The tumor suppressor p53 is a central regulator of cell fate in response to different types of insults. p53 protein recognizes specific structures in the DNA, dependent on sequence and structure. The focus of this work was analysis of the p53 structure-selective recognition of repeat sequences associated with human neurodegenerative diseases. The group studied how p53 and several deletion variants bound to repeat sequences folded into different shapes that occur in cells. They show that p53 binds to all studied DNA structures that are not the standard helical structure (non-B DNA structure), with a preference for structures formed by pyrimidine rich strands. They found a specific part of p53 to be crucial for recognition of such non-B DNA structures. They also observed that p53 prefers binding to the Pyrimidine-rich strand over the purine rich strand in non-B DNA from the repeat sequence in the first intron of the frataxin gene. The binding of p53 to this region was confirmed in human Friedreich's ataxia fibroblast and adenocarcinoma cells. Altogether these observations provide further evidence that p53 binds to non-B DNA structures in trinucleotide repeat sequences.
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