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To study the mechanism of RUNX1 and its mutants in DNA binding and altered gene expression

Shodhganga@INFLIBNET

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Title To study the mechanism of RUNX1 and its mutants in DNA binding and altered gene expression
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Contributor Saluja, Daman
 
Subject Biomedical Science
DNA
Gene
 
Description Runt related transcription factor 1 or RUNX1, though normally functions to
newlineregulate the development of hematopoietic system in concert with various
newlinetranscriptional co-regulators, its malfunction is known to be the major cause of
newlineseveral variants of acute leukemia. RUNX1 gene is the most common target
newlineof chromosomal translocations and mutations in its runt domain are frequently
newlineassociated with leukemogenesis. In mammalian system, in addition to
newlineRUNX1, two more genes comprise the family, namely RUNX2, which is
newlineessential for osteoblast differentiation and RUNX3, which is essential for the
newlineanti-proliferation and apoptosis of gastric epithelium, for differentiation of
newlinecertain root ganglion nerve cells, and for the establishment of mature CD8+
newlinecytotoxic T-lymphocytes. Structural studies of the runt domain of RUNX1-DNA
newlinecomplexes provide details of the direct contacts formed between the runt
newlinedomain of Runx1 and DNA. CBF., an interacting partner, hetero-dimerizes
newlinewith Runx1 and increases its affinity to bind with the DNA. The amino acid
newlineresidues, Lys83 and Arg174, of runt domain directly interact with the
newlineconsensus sequence of the promoters and found to be frequently mutated in
newlinethe leukemic patients. Most of the structure-functional studies, till date, are
newlineconfined to the binding of runt domain with synthetic DNA fragments of 8-10
newlinebp).
newlineTo understand the role of mutant RUNX1 in the progression of leukemia, an
newlineattempt was made to study the conformation of mutant protein using
newlinebiophysical parameters and physiological changes due to mutations in
newlineRUNX1 gene by analyzing the expression of direct/indirect target genes of
newlineRUNX1 in leukemic patients.
Bibliography p.176-192, Appendix p.193-196
 
Date 2014-04-28T11:22:31Z
2014-04-28T11:22:31Z
2014-04-28
n.d.
2012
n.d.
 
Type Ph.D.
 
Identifier http://hdl.handle.net/10603/18007
 
Language English US
 
Relation -
 
Rights university
 
Format 196p.
-
None
 
Coverage Biomedical Science
 
Publisher New Delhi
University of Delhi
Dept. of Medical Bio-Chemistry
 
Source INFLIBNET