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Protein plays unexpected role protecting chromosome tips
Date:8/13/2009

HOUSTON - A protein specialist that opens the genomic door for DNA repair and gene expression also turns out to be a multi-tasking workhorse that protects the tips of chromosomes and dabbles in a protein-destruction complex, a team lead by researchers at The University of Texas M. D. Anderson Cancer Center reports in the Aug. 13 edition of Molecular Cell.

"Instead of being a really important tool dedicated just to regulation of gene transcription, Gcn5 is more like a Swiss Army knife that performs different functions depending on what needs to be done in the cell," said senior author Sharon Dent, Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology.

The researchers document a chain of events that starts with depletion of Gcn5, which leads to decreased activity by another protein that protects yet a third protein from destruction. That last protein, TRF1, protects telomeres, dense structures at the end of chromosomes which, like the compressed plastic tips on the ends of a shoelace, keep the chromosome ends intact.

Variation in the gene that expresses the middle protein in this model, ubiquitin specific protease 22 (USP22), is part of an 11-gene signature associated with highly metastatic cancers and poor prognosis, the authors note.

"Our results indicate that the Gcn5 complex regulates not just gene transcription but also protein stability," Dent said. "They also suggest that the role of USP22 in highly aggressive cancers might be due to these new functions."

Telltale telomere damage

Chromosomes are made of DNA that is tightly intertwined with proteins called histones to form chromatin. Chromatin is a condensed structure that forms a natural barrier inhibiting access to DNA. Gcn5 was previously known for its role in a complex of proteins that loosens chromatin to allow access to DNA by the cell's DNA repair machinery and by transcription factors that launch t
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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