Rosenstiel Award 2012- Dr. Steven J. Elledge

The 2012 Rosenstiel award is being awarded to Dr. Steven J. Elledge of Harvard University and the Howard Hughes Medical Institute for his seminal contributions towards understanding the eukaryotic DNA damage response[1] [2] .
Cells are constantly challenged by damage to their DNA. It of no surprise therefore, that both prokaryotic and eukaryotic cells have evolved sophisticated and remarkably complex responses to deal with damaged DNA. It is for elucidating these mechanisms that Dr. Elledge is being honored with the Rosenstiel award this year.
Dr. Elledge’s interest with the DNA damage response began as a graduate student at MIT in the laboratory of Graham Walker, where he identified and cloned genes involved in DNA repair mechanism known as the SOS reponse in the bacterium E.coli[3, 4] . It was during this time that Dr. Elledge also invented an extremely useful molecular biology tool known as ‘phasmids’ which allowed for the ability to rapidly clone E.coli genes by packaging them in phages[5].
After MIT, Dr Elledge began his postdoctoral work at Stanford University where he discovered the Ribonucleotide reductase(RNR) genes in budding yeast[6, 7]. These genes are induced following DNA damage to promote the synthesis of deoxyribonucleotides which helps facilitate DNA repair. Dr. Elledge followed up on this work as a professor at Baylor University by a series of important papers that shed light on how cells arrest division after DNA damage. Most notably in 1994, his group identified the Rad53 checkpoint kinase that is activated after DNA damage and contributes to cell cycle arrest [8]. In 1998, his group also identified the mammalian homolog of Rad53 (Chk2) [9, 10].In 1999, the Elledge group reported that the DNA damage checkpoint in yeast occurs in two parallel pathways laying the foundation of our understanding of the DNA damage checkpoint[11]. More recently, work from the Elledge lab identified novel factors in the DNA damage response by performing a siRNA screen in mammalian cells[12].
Dr Steve Elledge has been an investigator of the Howard Hughes Medical Institute since 1993. In 2003 he moved to Harvard Medical School as Professor in the Departments of Genetics and as a Geneticist in the Department of Medicine, Brigham and Women’s Hospital. Dr. Elledge was elected in 2003 to both the U.S. National Academy of Sciences and the American Academy of Arts and Sciences. In addition to the Rosenstiel award, he has received the DAMD Breast Cancer Innovator Award (2003), the National Academy of Sciences Award in Molecular Biology (2002), the John B. Carter, Jr. Technology Innovation Award (2002), and the Paul Marks Prize for Cancer Research (2001[2]).

Editor’s Note: On Mar 20, 2013, Elledge was named to receive a 2013 Canada Gairdner International Award.

1. Brownlee, C., Biography of Stephen J. Elledge. Proc Natl Acad Sci U S A, 2004. 101(10): p. 3336-7.
2. Haber, J.E., The 2005 Genetics Society of America Medal. Steven J. Elledge. Genetics, 2005. 169(2): p. 506-7.
3. Elledge, S.J. and G.C. Walker, Proteins required for ultraviolet light and chemical mutagenesis. Identification of the products of the umuC locus of Escherichia coli. J Mol Biol, 1983. 164(2): p. 175-92.
4. Elledge, S.J. and G.C. Walker, The muc genes of pKM101 are induced by DNA damage. J Bacteriol, 1983. 155(3): p. 1306-15.
5. Elledge, S.J. and G.C. Walker, Phasmid vectors for identification of genes by complementation of Escherichia coli mutants. J Bacteriol, 1985. 162(2): p. 777-83.
6. Elledge, S.J. and R.W. Davis, Identification of the DNA damage-responsive element of RNR2 and evidence that four distinct cellular factors bind it. Mol Cell Biol, 1989. 9(12): p. 5373-86.
7. Elledge, S.J. and R.W. Davis, DNA damage induction of ribonucleotide reductase. Mol Cell Biol, 1989. 9(11): p. 4932-40.
8. Allen, J.B., et al., The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. Genes Dev, 1994. 8(20): p. 2401-15.
9. Hirao, A., et al., DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science, 2000. 287(5459): p. 1824-7.
10. Matsuoka, S., M. Huang, and S.J. Elledge, Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science, 1998. 282(5395): p. 1893-7.
11. Sanchez, Y., et al., Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science, 1999. 286(5442): p. 1166-71.
12. Adamson, B., et al., A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response. Nat Cell Biol, 2012. 14(3): p. 318-28.

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