A Large-Scale Screen for Mutagen-Sensitive Loci in Drosophila

doi:10.1534/genetics.167.1.217

A Large-Scale Screen for Mutagen-Sensitive Loci in Drosophila

Anne Laurencon^a,b, Charisse M. Orme^a,c, Heather K. Peters^a,c, Christina L. Boulton^a,d, Eszter K. Vladar^a,e, Sasha A. Langley^a, Emmanuel P. Bakis^a, David T. Harris^a,c, Nathan J. Harris^a, Sarah M. Wayson^a, R. Scott Hawley^a,c, and Kenneth C. Burtis^a
^a Section of Molecular and Cellular Biology, University of California, Davis, California 95616,
^b Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard Lyon 1/UMR 5534, 69622 Villeurbanne Cedex, France,
^c Stowers Institute for Medical Research, Kansas City, Missouri 64110,
^d Howard Hughes Medical Institute, Harvard Institutes of Medicine, Boston, Massachusetts 02115
^e Department of Genetics, Stanford University School of Medicine, Palo Alto, California 94305

Corresponding author: Kenneth C. Burtis, 1 Shields Ave., University of California, Davis, CA 95616., kcburtis{at}ucdavis.edu (E-mail)

Communicating editor: K. G. GOLIC

In a screen for new DNA repair mutants, we tested 6275 Drosophilastrains bearing homozygous mutagenized autosomes (obtained fromC. Zuker) for hypersensitivity to methyl methanesulfonate (MMS)and nitrogen mustard (HN2). Testing of 2585 second-chromosomelines resulted in the recovery of 18 mutants, 8 of which werealleles of known genes. The remaining 10 second-chromosome mutantswere solely sensitive to MMS and define 8 new mutagen-sensitivegenes (mus212–mus219). Testing of 3690 third chromosomesled to the identification of 60 third-chromosome mutants, 44of which were alleles of known genes. The remaining 16 mutantsdefine 14 new mutagen-sensitive genes (mus314–mus327).We have initiated efforts to identify these genes at the molecularlevel and report here the first two identified. The HN2-sensitivemus322 mutant defines the Drosophila ortholog of the yeast snm1gene, and the MMS- and HN2-sensitive mus301 mutant defines theDrosophila ortholog of the human HEL308 gene. We have also identifieda second-chromosome mutant, mus215^ZIII-2059, that uniformlyreduces the frequency of meiotic recombination to <3% ofthat observed in wild type and thus defines a function requiredfor both DNA repair and meiotic recombination. At least oneallele of each new gene identified in this study is availableat the Bloomington Stock Center.

This article has been cited by other articles:

D. S. Wei and Y. S. Rong
A Genetic Screen For DNA Double-Strand Break Repair Mutations in Drosophila
Genetics, September 1, 2007; 177(1): 63 - 77.
[Abstract] [Full Text] [PDF]

U. Abdu, M. Klovstad, V. Butin-Israeli, A. Bakhrat, and T. Schupbach
An essential role for Drosophila hus1 in somatic and meiotic DNA damage responses
J. Cell Sci., March 15, 2007; 120(6): 1042 - 1049.
[Abstract] [Full Text] [PDF]

R. McCaffrey, D. St Johnston, and A. Gonzalez-Reyes
Drosophila mus301/spindle-C Encodes a Helicase With an Essential Role in Double-Strand DNA Break Repair and Meiotic Progression
Genetics, November 1, 2006; 174(3): 1273 - 1285.
[Abstract] [Full Text] [PDF]

C. P. Guy and E. L. Bolt
Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands
Nucleic Acids Res., June 30, 2005; 33(11): 3678 - 3690.
[Abstract] [Full Text] [PDF]

N. Shima, R. J. Munroe, and J. C. Schimenti
The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm
Mol. Cell. Biol., December 1, 2004; 24(23): 10381 - 10389.
[Abstract] [Full Text] [PDF]

E. J. Koundakjian, D. M. Cowan, R. W. Hardy, and A. H. Becker
The Zuker Collection: A Resource for the Analysis of Autosomal Gene Function in Drosophila melanogaster
Genetics, May 1, 2004; 167(1): 203 - 206.
[Abstract] [Full Text] [PDF]

B. T. Wakimoto, D. L. Lindsley, and C. Herrera
Toward a Comprehensive Genetic Analysis of Male Fertility in Drosophila melanogaster
Genetics, May 1, 2004; 167(1): 207 - 216.
[Abstract] [Full Text] [PDF]

				U. Abdu, M. Klovstad, V. Butin-Israeli, A. Bakhrat, and T. Schupbach An essential role for Drosophila hus1 in somatic and meiotic DNA damage responses J. Cell Sci., March 15, 2007; 120(6): 1042 - 1049. [Abstract] [Full Text] [PDF]

				R. McCaffrey, D. St Johnston, and A. Gonzalez-Reyes Drosophila mus301/spindle-C Encodes a Helicase With an Essential Role in Double-Strand DNA Break Repair and Meiotic Progression Genetics, November 1, 2006; 174(3): 1273 - 1285. [Abstract] [Full Text] [PDF]

				C. P. Guy and E. L. Bolt Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands Nucleic Acids Res., June 30, 2005; 33(11): 3678 - 3690. [Abstract] [Full Text] [PDF]

				N. Shima, R. J. Munroe, and J. C. Schimenti The Mouse Genomic Instability Mutation chaos1 Is an Allele of Polq That Exhibits Genetic Interaction with Atm Mol. Cell. Biol., December 1, 2004; 24(23): 10381 - 10389. [Abstract] [Full Text] [PDF]

				E. J. Koundakjian, D. M. Cowan, R. W. Hardy, and A. H. Becker The Zuker Collection: A Resource for the Analysis of Autosomal Gene Function in Drosophila melanogaster Genetics, May 1, 2004; 167(1): 203 - 206. [Abstract] [Full Text] [PDF]

				B. T. Wakimoto, D. L. Lindsley, and C. Herrera Toward a Comprehensive Genetic Analysis of Male Fertility in Drosophila melanogaster Genetics, May 1, 2004; 167(1): 207 - 216. [Abstract] [Full Text] [PDF]