The oncofetal protein HMGA2 influences telomere stability in cancer cells.
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Date
2014-08-08
Authors
Gim, Jeonga
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Abstract
HMGA2 is a non-histone chromatin binding protein which binds to the adenine-thymine (AT)
rich regions of DNA. HMGA2 is expressed in fetal tissues and its expression is downregulated
through the microRNA let-7 in normal adult somatic tissues. Cancer cells frequently re-express
the oncofetal protein HMGA2. HMGA2 has various functions related to neoplasm, including
cancer transformation, epithelial-to-mesenchymal transition, aiding metastasis, and
chemoresistance; all of which leads to poor prognosis for cancer patients. HMGA2 interacts
with ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related kinase
(ATR) in the DNA damage signaling pathways and was shown to promote DNA damage repair.
Thus, HMGA2 has a cytoprotective role against DNA damage and enhances cell survival.
HMGA2 was shown to be present at telomeres, but its functional role at telomeres is not fully
understood. Telomeres are nucleotide repeats located at the end of a chromosome. They are
protected from being recognized as DNA damage sites by the shelterin complex consisting of
six proteins. Preliminary data in the Hombach/Klonisch lab indicate that HMGA2 interacts with
one of shelterin complex proteins. We hypothesized that HMGA2 has a protective function on
telomeres and reduces telomere instability upon DNA damage. Telomere dysfunction was
assessed by detection of anaphase chromatin bridges and micronuclei. We compared cancer
cells with and without expression of HMGA2. Indeed, we have confirmed that HMGA2 helps to
stabilize telomeres. However, our experimental conditions did not show alterations in telomere
instability after induction of DNA damage.
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Keywords
HMGA2, telomere stability