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Last Updated: Aug 19th, 2006 - 22:18:38

Genetics Channel
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Latest Research : Genetics

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Scientists Uncover Rules for Gene Amplification
Jun 30, 2006, 13:17, Reviewed by: Dr. Priya Saxena

“If these rules operating in yeast can be extended to higher eukaryotes then we can propose that if the oncogene is located between the hairpin-capped break and the telomere, then the amplification event will result in a double minute. If the break occurs between the oncogene and the telomere, then the amplification would yield a homogenously-staining region.”

 
Gene amplification plays an important role in causing cancers via activation of oncogenes. If scientists can determine the rules as to which segments of genetic material become amplified and how, oncologists and drug researchers may be able to interrupt that process and prevent the formation and growth of some tumors. Using yeast as a model organism, researchers at the Georgia Institute of Technology have discovered that the location of a hairpin-capped break relative to the end of the chromosome will determine the fate of the amplification event.

Gene amplification is the increase in copy number of a particular piece of DNA and
is a hallmark of tumor cells. Amplified genomic segments are frequently manifested in one of two cytologically recognizable forms. Double minutes are extrachromosomal segments of amplified DNA. Homogeneously staining regions are amplified intrachromosomal segments forming large genomic regions. Some strategies of pharmaceutical research in cancer prevention and treatment could involve curbing cancer development via restricting gene amplification. The first step towards achieving this is to discover the rules that govern whether an amplification event is a double minute or a homogenously-staining region.

It’s known that regions of chromosomes that are prone to amplification have
palindromic sequences of DNA, which are weak places where the chromosome can break. These palindromic sequences can be naturally found in human genome. The distribution of such sequences can vary from one individual to another. Researchers at the Georgia Institute of Technology have discovered that a particular type of DNA break, a hairpin-capped double strand break, induced by these palindromic sequences, is a precursor to amplification.

“We have a developed a system in yeast which would mimic the situation in human cancer cells wherein oncogenes might be located next to palindromic sequences. Using this system we have discovered the rules that determine how double minutes or homogeneously staining regions can be generated,” said Kirill Lobachev, assistant professor in Georgia Tech’s School of Biology.

“If these rules operating in yeast can be extended to higher eukaryotes then we can propose that if the oncogene is located between the hairpin-capped break and the telomere, then the amplification event will result in a double minute. If the break occurs between the oncogene and the telomere, then the amplification would yield a homogenously-staining region.” adds Vidhya Narayanan a Ph.D. student in Kirill Lobachev’s lab and first author of the study.

The findings can help researchers understand the cause of cancer in diseased individuals and also to potentially identify individuals who might be prone for cancer.

In addition to Lobachev and Narayanan, the research team consisted of Hyun-Min Kim from Georgia Tech and collaborators Piotr A. Mieczkowski and Thomas D. Petes from Duke University. This work was supported by funds from National Science Foundation and National Institute of Health.
 

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In addition to Lobachev and Narayanan, the research team consisted of Hyun-Min Kim from Georgia Tech and collaborators Piotr A. Mieczkowski and Thomas D. Petes from Duke University. This work was supported by funds from National Science Foundation and National Institute of Health.

The Georgia Institute of Technology is one of the nation's premiere research universities. Ranked ninth among U.S. News & World Report's top public universities, Georgia Tech educates more than 17,000 students every year through its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Tech maintains a diverse campus and is among the nation's top producers of women and African-American engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute. During the 2004-2005 academic year, Georgia Tech reached $357 million in new research award funding. The Institute also maintains an international presence with campuses in France and Singapore and partnerships throughout the world.


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