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quency of endogenous Htt is neurons is still missing, but pre-
sence of polyA or polyS proteins in HD-affected brain tissues
(17) and the intrinsic high propensity of frameshifting in neurons
(23) support the notion, that frameshifting may accompany HD
pathology. The striatum is an early target of HD, and striatum has
one of the lowest tRNAGln-CUG concentrations among the brain
regions of mouse. Furthermore, the CAG repeats have the highest
instability in striatum; the CAG stretches are by approximately
10 codons larger than the CAG repeats in any other tissue of the
same individual (24). Thus, is it conceivable to think that the
combination of expanded CAG stretches and the lower tRNAGln-
CUG household would potentiate the frequency of frameshifting
of expanded CAG repeats in striatum. Thus, frameshifting within
expanded CAG stretches may act as modifer of HD pathology
and may contribute to the heterogeneity in disease course and
onset on both cellular level and single individual.
References
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Zoya Ignatova did her PhD in Hamburg
with Prof. Dr. Volker Kasche. After her
post-doctoral research at the University
of Massachusetts, she joined the Max-
Planck Institute of Biochemistry in Mar-
tiensried as an Independent Junior group
leader. In 2008 she was appointed as a
Professor in Biochemistry at the Univer-
sity of Potsdam.
research news
Figure 4. Disbalance between the demand and supply for glutaminyl-
tRNAGln-CUG alters translation of repetitive CAG stretche:
Abnormal expansion of CAG repeats, over the HD disease threshold,
increases disproportionally the demand of glutaminyl-tRNAGln-CUG which
causes translational frameshift within the CAG stretch.
Paul Saffert joined the Ignatova Lab in
2010 for his Master thesis and continued
with the PhD. He studied Biochemistry at
the University of Potsdam where he also
received his Bachelor of Science.
Paul Saffert and Zoya Ignatova:
Biochemistry, University of Potsdam,
Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
Correspondence to: Paul Saffert,
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