THESIS
2016
xi, 52 pages : illustrations (some color) ; 30 cm
Abstract
As the first step of gene expression, accurate transcription is essential to keep normal
translation and the functions of proteins. Human mitochondrial RNA polymerase (POLRMT,
for short), which exists in human mitochondria, is responsible for transcription of 13 subunits
of the oxidative phosphorylation complexes, 2 ribosomal RNAs (rRNAs) and 22 transfer
RNAs (tRNAs). POLRMT has the highest sequence similarity to bacteriophage T7 RNA
polymerase, although it seems that the transcription elongation mechanism of POLRMT is
much similar to that of nucleus RNA polymerase II (Pol II). In fact, there are also a few
differences between the mitochondrial and the nucleus transcription elongations. First, distinct
transcription elongation factors are present in mitochondria. For example, TE...[
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As the first step of gene expression, accurate transcription is essential to keep normal
translation and the functions of proteins. Human mitochondrial RNA polymerase (POLRMT,
for short), which exists in human mitochondria, is responsible for transcription of 13 subunits
of the oxidative phosphorylation complexes, 2 ribosomal RNAs (rRNAs) and 22 transfer
RNAs (tRNAs). POLRMT has the highest sequence similarity to bacteriophage T7 RNA
polymerase, although it seems that the transcription elongation mechanism of POLRMT is
much similar to that of nucleus RNA polymerase II (Pol II). In fact, there are also a few
differences between the mitochondrial and the nucleus transcription elongations. First, distinct
transcription elongation factors are present in mitochondria. For example, TEFM
(transcription elongation factor, mitochondria), which is a unique transcription factor in
mitochondria can facilitate transcription elongation by interacting with POLRMT elongation
complex. Second, mitochondrial DNA is more susceptible to DNA damages due to lack of
nucleosome as well as of certain DNA repair mechanisms. Therefore, POLRMT has to go
through damaged DNA more frequently. Here, we study the effects of DNA damages and
transcription factors on mitochondrial transcription elongation. We found that POLRMT stalls
at the Cisplatin and 8-oxoguanine DNA damage sites and some of these pauses/stalls can be
enhanced by TFAM (transcription repression factor) and can be rescued by TEFM. We will
expand these finding to understand the transcription elongation dynamics of POLRMT in the
presence of DNA damages as well as mitochondrial transcription elongation factors by
single-molecule and real-time machine--optical tweezers.
Key words: POLRMT, Transcription Elongation, Transcription Factors, Optical Tweezers,
Dynamics
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