Friday, October 28, 2011

How – and when – to make a protein


Paul C. Zamecnik, MD, was associated with the MGH for more than 50 years. During that time, he made several fundamental discoveries related to how and when the genetic code carried in DNA is translated into protein molecules. In the mid-1950s he and his MGH colleague Mahlon Hoagland, MD, helped reveal a key step in the process when they discovered that the amino acids required to construct a protein strand were carried to the site of protein assembly by small RNA segments called transfer RNA.  Two decades later Zamecnik developed a way to block the expression of specific genes with what is now known as antisense technology – special single-stranded DNA that binds to and interferes with translation of segments of RNA.  

Zamecnik’s work was honored with the Warren Triennial Prize three times: in 1946 and 1949 – before he joined the MGH staff – and again in 1998. He also received a Lasker Award in 1996. Upon Zamecnik’s death in 2009, just a few months after he stopped working in his MGH lab, Dennis Ausiello, MD,  capchief of the Department of Medicine, noted that among Zamecnik’s colleagues were “many Nobel laureates who quite frankly felt he should have been among them.”

Since each cell in the body contains the full complement of DNA an organism has inherited, exactly what kind of cell it is and how it develops and functions depend on which genes are turned on – allowing their encoded proteins to be produced – and which remain silent. A research team led by Robert Kingston, PhD, chief of the Department of Molecular Biology, is investigating fundamental mechanisms that control whether particular genes are turned on or off.  

Within a cell’s nucleus, strands of DNA are wrapped around proteins called histones to form nucleosomes – bead-on-a-string structures that incorporate most of the DNA strandsDNA segments in regions with widely spaced, loosely wrapped nucleosomes can be easily accessed by the enzymes involved in reading the genetic code, thereby turning the gene on. But genes in tightly packed nucleosomes are inaccessible and remain silent. Kingston’s group is investigating exactly how the nucleosome structure is either opened up or packaged more tightly to regulate gene expression.

Read more articles from the 10/28/11 Hotline issue.


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