The 2009 Novitski Prize: Rodney Rothstein and Kent Golic

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					                                                  Honors and Awards                                               837


                                          The 2009 Novitski Prize

                                   Rodney Rothstein and Kent Golic




                   Rodney Rothstein                                                Kent Golic



T    HE Novitski Prize, established in 2008 by the family
      of the remarkable geneticist Ed Novitski, is
awarded for innovative experimental approaches and
                                                             et al. 1982). Being able to direct the integration by
                                                             linearizing the plasmid with a restriction endonuclease
                                                             made these approaches far more efficient (Orr-
extraordinary creativity in solving a significant problem     Weaver et al. 1981). But it was Rothstein’s ‘‘ends-out’’
in genetics research. The 2009 Novitski Prize honors         transformation procedure, modestly published in
two pioneers of gene targeting, Rodney Rothstein of          Methods in Enzymology (Rothstein 1983), that
Columbia University and Kent Golic of the University of      revolutionized yeast gene targeting (Figure 1A). Exactly
Utah. The development of transformation in budding           how the transformed linearized DNA replaces homol-
yeast by Hinnen et al. (1978) made it possible to clone      ogous sequences on a chromosome is not yet fully
genes by complementation and raised the prospect that        understood, even if one liberates a fragment inside the
one could also delete or mutate genes selectively. Rod       nucleus from another site within the genome (Leung
Rothstein contributed two fundamental ideas to our           et al. 1997; Negritto et al. 1997; Langston and
current ability to knock out genes and to knock in           Symington 2004); but in budding yeast, gene re-
specific mutations. First, in collaboration with Terry        placement is a surprisingly accurate process. The ease
Orr-Weaver and Jack Szostak, Rothstein demonstrated          with which deletions and targeted mutations could be
that a double-strand break within a yeast gene sequence      accomplished made it possible to create collections of
on a plasmid dramatically increases the likelihood of        deletions of every open reading frame in budding yeast,
the plasmid integrating at the homologous site on a          along with ways to insert epitope tags, GFP fusions, and
chromosome (Orr-Weaver et al. 1981, 1983). These ex-         temperature-sensitive degrons. Rothstein’s simple idea
periments provided much of the impetus for de-               was later extended to gene knock-out technology in
veloping a comprehensive double-strand-break-repair          mammalian cells, earning Oliver Smithies and Mario
model of recombination (Szostak et al. 1983). But            Cappecchi the 2007 Nobel Prize in Physiology and
Rothstein’s interest was also focused on methods to          Medicine.
create specific mutations in yeast. The earliest strategy        Despite these advances in yeast and in mammalian
to knock out a gene was to integrate a mutated gene          cells, gene targeting in Drosophila remained elusive,
sequence on a plasmid into the chromosome, creating          even a decade after yeast targeting had become routine.
a duplication, and then to select or screen for excision     Spradling and Rubin (1982) showed that P elements
events that reversed the integration but left the mutant     could be mobilized to create germline mutations but
sequence behind (Scherer and Davis 1979). An                 attempts to transform the germline with linearized DNA
alternative strategy was to integrate a segment of the       fragments carrying a selectable marker failed. Kent
gene lacking its 59- and 39-ends, thus creating two          Golic had succeeded in expressing the yeast site-specific
tandem and truncated copies of the gene (Shortle             recombinase FLP in flies, allowing it to direct reciprocal
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DOCUMENT INFO
Description: [...] in collaboration with Terry Orr-Weaver and Jack Szostak, Rothstein demonstrated that a double-strand break within a yeast gene sequence on a plasmid dramatically increases the likelihood of the plasmid integrating at the homologous site on a chromosome (Orr-Weaver et al. 1981, 1983).
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