![]() (It is, in fact, to this point the only known human transposable element.) She studied the precise mechanism whereby LINE-1 replicates and disperses copies to new locations along the genome. Focusing on LINE-1, a DNA sequence repeated and interspersed thousands of times in human chromosomal DNA, Singer concluded that it is capable of transposition, or movement and insertion into new places on chromosomal DNA. Singer had begun to focus on a large family of repeated stretches of mammalian DNA called LINEs, or long interspersed nucleotide elements, that are present with very little variation in the genomes of all mammals. ![]() Singer's most important discovery since her contribution towards deciphering the genetic code came in the 1980s, even though, as head of the large Laboratory of Biochemistry at the National Cancer Institute, she was spending more than half of her time on administration and support of her laboratory's 15 research groups. Throughout the 1960s, Singer continued her work in nucleic acid enzymology, specifically on the action of polynucleotide phosphorylase. ![]() By matching each amino acid to a particular triplet of RNA bases, these scientists laid open the dictionary of three-letter words in which the genetic code is written. Singer played a key role in these experiments, producing RNA molecules with specific, predetermined base sequences that over the next four years Nirenberg and others showed could specify all of the twenty amino acids. Nirenberg's finding that triplets of uracil coded for phenylalanine represented the first step in cracking the genetic code. This cell-free system enabled Nirenberg and his coworker Heinrich Matthaei to show in 1961 that an RNA molecule made up entirely of triplets of the base uracil-polyuridylic acid, or poly-U-spurred the synthesis of a polypeptide chain composed entirely of phenylalanine, one of the twenty common amino acids that make up proteins. This result lent support to the thesis that RNA plays a key role in using genetic information from DNA to direct the synthesis of proteins. The RNA then strung these amino acids together into a polypeptide chain, the precursor of a protein. Over several years Singer and Heppel accumulated a library of artificial polyribonucleotides: strings of RNA in which all the bases were identical-all uracil, for example-or in which two bases, such as uracil and cytosine, alternated in random order, or in which the end of the string had a different composition from the rest.Īt the same time, Heppel and a few other scientists at NIAMDD, in particular the biochemist Marshall Nirenberg, were adding RNA extracted from cells to solutions containing free amino acids, the chemical components of proteins. Knowledge of the sequence of these polyribonucleotides enabled Heppel and Singer not only to understand how the enzyme catalyzed their synthesis, but also to make artificial RNAs of different defined compositions. In particular, he had developed techniques of electrophoresis and paper chromatography for analyzing the base compositions-the sequence of the four chemical bases of RNA-of the polyribonucleotides he was producing with the help of polynucleotide phosphorylase. This enzyme strings together individual nucleotides into random strands of RNA, known as polyribonucleotides. Heppel was one of the first scientists to investigate the synthesis of RNA and DNA in vitro by using polynucleotide phosphorylase, an enzyme discovered by Severo Ochoa and Marianne Grunberg-Manago. As a new postdoctoral researcher in Leon Heppel's laboratory at the National Institute of Arthritis, Metabolism, and Digestive Diseases (NIAMDD) at the National Institutes of Health, Singer participated in research into the role of enzymes that regulate the synthesis of nucleic acids.
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