Understanding of HMGB1 protein involvement in maintaining genome stability

Investor logo
Project Identification
GA204/08/1530
Project Period
1/2008 - 12/2010
Investor / Pogramme / Project type
Czech Science Foundation
MU Faculty or unit
Faculty of Science
Keywords
x
Cooperating Organization
Institute of Biophysics

HMGB1 is a relatively abundant chromatin-associated protein and recent data indicated striking chromosomal instability in HMGB1 knock-outed primary mouse embryonic fibroblasts. One mechanism for chromosome instability is through the dysfunction of telomeres, the specific nucleoprotein structures forming chromosome ends and protecting them from recombination and degradation. Recently we have discovered that deficiency of HMGB1 in mouse cells resulted in lower telomerase activity, general telomere shortening or loss, and occasional telomere expansions. We have also identified HMGB1 as a telomerase-associated protein in vitro. As most, if not all, tumor cells over-express HMGB1, deregulated expression of HMGB1 could have catastrophic consequences for the structure of telomeres. In this project we intend to study the impact of aberrant HMGB1 expression (silencing or over-expression) in human cells with different status of tumor suppressor protein p53 on: (i) the activity of telomerase; (ii) the

Publications

Total number of publications: 8


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