ISOLATION AND CHARACTERIZATION OF X-LINKED MUTANTS OF DROSOPHILA MELANOGASTER WHICH ARE SENSITIVE TO MUTAGENS

J. B. Boyd ¹, M. D. Golino ¹, T. D. Nguyen ¹, and M. M. Green ¹

¹ Department of Genetics, University of California, Davis, California 95616

Thirteen X-linked mutants have been isolated in Drosophila melanogaster which render male and homozygous female larvae sensitive to the mutagen methyl methanesulfonate. Their characterization and preliminary assignment to functional groups is described. Four of these mutants are alleles of mei-41 (Baker and Carpenter 1972). Like previously isolated alleles of this locus, these mutants reduce fertility and increase loss and nondisjunction of the X-chromosome in homozygous females. The remaining mutants have been tentatively assigned to six functional groups (two mutants to the mus(1)101 locus, two to mus(1)102 , two to mus(1)103, and one each to mus(1)104, mus(1)105 , and mus(1)106). Several of the complementation groups can be distinguished on the basis of nondisjunction and cross sensitivity to mutagens. Females homozygous for the mei-41, mus(1)101 and mus(1)102 mutants exhibit elevated levels of nondisjunction. Mutants belonging to complementation groups mei-41, mus(1)101, and mus(1)104 are sensitive to nitrogen mustard (HN2) in addition to their MMS sensitivity. Among these mutants there is currently a direct correlation between sensitivity to HN2, sensitivity to 2-acetylaminofluorene and a deficiency in post-replication repair ( Boyd and Setlow 1976). Only the mei-41 mutants are hypersensitive to UV radiation, although several of the mutants exhibit sensitivity to -rays. Semidominance is observed in female larvae of the mei-41, mus(1)104, and mus(1)103 mutants after exposure to high concentrations of MMS. The properties of the mutants generally conform to a pattern which has been established for related mutants in yeast. Additional properties of these mutants are summarized in Table 9.

This article has been cited by other articles:

				J. D. Richards, K. A. Johnson, H. Liu, A.-M. McRobbie, S. McMahon, M. Oke, L. Carter, J. H. Naismith, and M. F. White Structure of the DNA Repair Helicase Hel308 Reveals DNA Binding and Autoinhibitory Domains J. Biol. Chem., February 22, 2008; 283(8): 5118 - 5126. [Abstract] [Full Text] [PDF]

				K. Trowbridge, K. McKim, S. J. Brill, and J. Sekelsky Synthetic Lethality of Drosophila in the Absence of the MUS81 Endonuclease and the DmBlm Helicase Is Associated With Elevated Apoptosis Genetics, August 1, 2007; 176(4): 1993 - 2001. [Abstract] [Full Text] [PDF]

				J. R. LaRocque, D. L. Dougherty, S. K. Hussain, and J. Sekelsky Reducing DNA Polymerase {alpha} in the Absence of Drosophila ATR Leads to P53-Dependent Apoptosis and Developmental Defects Genetics, July 1, 2007; 176(3): 1441 - 1451. [Abstract] [Full Text] [PDF]

				J. R. LaRocque, B. Jaklevic, T. T. Su, and J. Sekelsky Drosophila ATR in Double-Strand Break Repair Genetics, March 1, 2007; 175(3): 1023 - 1033. [Abstract] [Full Text] [PDF]

				J.-E. Kim, S. A. McAvoy, D. I. Smith, and J. Chen Human TopBP1 Ensures Genome Integrity during Normal S Phase Mol. Cell. Biol., December 15, 2005; 25(24): 10907 - 10915. [Abstract] [Full Text] [PDF]

				N. R. May, M. Thomer, K. F. Murnen, and B. R. Calvi Levels of the origin-binding protein Double parked and its inhibitor Geminin increase in response to replication stress J. Cell Sci., September 15, 2005; 118(18): 4207 - 4217. [Abstract] [Full Text] [PDF]

				S. J. Radford, E. Goley, K. Baxter, S. McMahan, and J. Sekelsky Drosophila ERCC1 Is Required for a Subset of MEI-9-Dependent Meiotic Crossovers Genetics, August 1, 2005; 170(4): 1737 - 1745. [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]

				A. H. Holway, C. Hung, and W. M. Michael Systematic, RNA-Interference-Mediated Identification of mus-101 Modifier Genes in Caenorhabditis elegans Genetics, March 1, 2005; 169(3): 1451 - 1460. [Abstract] [Full Text] [PDF]

				A. Laurencon, C. M. Orme, H. K. Peters, C. L. Boulton, E. K. Vladar, S. A. Langley, E. P. Bakis, D. T. Harris, N. J. Harris, S. M. Wayson, et al. A Large-Scale Screen for Mutagen-Sensitive Loci in Drosophila Genetics, May 1, 2004; 167(1): 217 - 231. [Abstract] [Full Text] [PDF]

				O. Yildiz, H. Kearney, B. C. Kramer, and J. J. Sekelsky Mutational Analysis of the Drosophila DNA Repair and Recombination Gene mei-9 Genetics, May 1, 2004; 167(1): 263 - 273. [Abstract] [Full Text] [PDF]

				E. R. Parrilla-Castellar and L. M. Karnitz Cut5 Is Required for the Binding of Atr and DNA Polymerase {alpha} to Genotoxin-damaged Chromatin J. Biol. Chem., November 14, 2003; 278(46): 45507 - 45511. [Abstract] [Full Text] [PDF]

				S. Symphorien and R. C. Woodruff Effect of DNA Repair on Aging of Transgenic Drosophila melanogaster: I. mei-41 Locus J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2003; 58(9): B782 - 787. [Abstract] [Full Text] [PDF]

				S. Cohen, K. Yacobi, and D. Segal Extrachromosomal Circular DNA of Tandemly Repeated Genomic Sequences in Drosophila Genome Res., June 1, 2003; 13(6): 1133 - 1145. [Abstract] [Full Text] [PDF]

				A. Laurencon, A. Purdy, J. Sekelsky, R. S. Hawley, and T. T. Su Phenotypic Analysis of Separation-of-Function Alleles of MEI-41, Drosophila ATM/ATR Genetics, June 1, 2003; 164(2): 589 - 601. [Abstract] [Full Text] [PDF]

				R. A. Van Hatten, A. V. Tutter, A. H. Holway, A. M. Khederian, J. C. Walter, and W. M. Michael The Xenopus Xmus101 protein is required for the recruitment of Cdc45 to origins of DNA replication J. Cell Biol., November 25, 2002; 159(4): 541 - 547. [Abstract] [Full Text] [PDF]

				R. R. Yamamoto, J. M. Axton, Y. Yamamoto, R. D. C. Saunders, D. M. Glover, and D. S. Henderson The Drosophila mus101 Gene, Which Links DNA Repair, Replication and Condensation of Heterochromatin in Mitosis, Encodes a Protein With Seven BRCA1 C-Terminus Domains Genetics, October 1, 2000; 156(2): 711 - 721. [Abstract] [Full Text]

				M. H. Brodsky, J. J. Sekelsky, G. Tsang, R. S. Hawley, and G. M. Rubin mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development Genes & Dev., March 15, 2000; 14(6): 666 - 678. [Abstract] [Full Text]

				A. Kasravi, M. F. Walter, S. Brand, J. M. Mason, and H. Biessmann Molecular Cloning and Tissue-Specific Expression of the mutator2 Gene (mu2) in Drosophila melanogaster Genetics, July 1, 1999; 152(3): 1025 - 1035. [Abstract] [Full Text]

				C. Flores and W. Engels Microsatellite instability in Drosophila spellchecker1 (MutS homolog) mutants PNAS, March 16, 1999; 96(6): 2964 - 2969. [Abstract] [Full Text] [PDF]

				J. J. Sekelsky, K. C. Burtis, and R. S. Hawley Damage Control: The Pleiotropy of DNA Repair Genes in Drosophila melanogaster Genetics, April 1, 1998; 148(4): 1587 - 1598. [Abstract] [Full Text] [PDF]

				A. Bhui-Kaur, M. F. Goodman, and J. Tower DNA Mismatch Repair Catalyzed by Extracts of Mitotic, Postmitotic, and Senescent Drosophila Tissues and Involvement of mei-9 Gene Function for Full Activity Mol. Cell. Biol., March 1, 1998; 18(3): 1436 - 1443. [Abstract] [Full Text]

				K S Keegan, D A Holtzman, A W Plug, E R Christenson, E E Brainerd, G Flaggs, N J Bentley, E M Taylor, M S Meyn, S B Moss, et al. The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes. Genes & Dev., October 1, 1996; 10(19): 2423 - 2437. [Abstract] [PDF]

				E L Beall and D C Rio Drosophila IRBP/Ku p70 corresponds to the mutagen-sensitive mus309 gene and is involved in P-element excision in vivo. Genes & Dev., April 15, 1996; 10(8): 921 - 933. [Abstract] [PDF]

				M Gatti, D. Smith, and B. Baker A gene controlling condensation of heterochromatin in Drosophila melanogaster Science, July 1, 1983; 221(4605): 83 - 85. [Abstract] [PDF]

				M. Resnick, J. Kasimos, J. Game, R. Braun, and R. Roth Changes in DNA during meiosis in a repair-deficient mutant (rad 52) of yeast Science, May 1, 1981; 212(4494): 543 - 545. [Abstract] [PDF]