Originally published as Genetics Published Articles Ahead of Print on March 2, 2005.

Genetics, Vol. 170, 161-171, May 2005, Copyright © 2005
doi:10.1534/genetics.104.036343

Synthetic Lethality of Retinoblastoma Mutant Cells in the Drosophila Eye by Mutation of a Novel Peptidyl Prolyl Isomerase Gene

Kyle A. Edgar^*,1, Marcia Belvin^*,1,2,3, Annette L. Parks^*,4, Kellie Whittaker^*, Matt B. Mahoney^*,5, Monique Nicoll^*, Christopher C. Park^*,6, Christopher G. Winter^*, Feng Chen^*,7, Kim Lickteig^*,8, Ferhad Ahmad^*, Hanife Esengil^*,9, Matthew V. Lorenzi, Amanda Norton^*,10, Brent A. Rupnow, Laleh Shayesteh^*, Mariano Tabios^*, Lynn M. Young^*,11, Pamela M. Carroll^,12, Casey Kopczynski^*,13, Gregory D. Plowman^*,3, Lori S. Friedman^*,3 and Helen L. Francis-Lang^*

^* Exelixis, South San Francisco, California 94083
Oncology Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543
Applied Genomics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543

² Corresponding author: Genentech, 1 DNA Way, Bldg. 11, MS215, South San Francisco, CA 94080.
E-mail: mbelvin{at}gene.com

Mutations that inactivate the retinoblastoma (Rb) pathway are common in human tumors. Such mutations promote tumor growth by deregulating the G1 cell cycle checkpoint. However, uncontrolled cell cycle progression can also produce new liabilities for cell survival. To uncover such liabilities in Rb mutant cells, we performed a clonal screen in the Drosophila eye to identify second-site mutations that eliminate Rbf^– cells, but allow Rbf⁺ cells to survive. Here we report the identification of a mutation in a novel highly conserved peptidyl prolyl isomerase (PPIase) that selectively eliminates Rbf^– cells from the Drosophila eye.

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