The Drosophila melanogaster DNA Ligase IV Gene Plays a Crucial Role in the Repair of Radiation-Induced DNA Double-Strand Breaks and Acts Synergistically with Rad54

Marcin M. Gorski, J. C J Eeken, A. W M De Jong, Ilse Klink, Marjan Loos, Ron J. Romeijn, Bert L. Van Veen, Leon H. Mullenders, Wouter Ferro, Albert Pastink

Research output: Contribution to journalArticle

Abstract

DNA Ligase IV has a crucial role in double-strand break (DSB) repair through nonhomologous end joining (NHEJ). Most notably, its inactivation leads to embryonic lethality in mammals. To elucidate the role of DNA Ligase IV (Lig4) in DSB repair in a multicellular lower eukaryote, we generated viable Lig4-deficient Drosophila strains by P-element-mediated mutagenesis. Embryos and larvae of mutant lines are hypersensitive to ionizing radiation but hardly so to methyl methanesulfonate (MMS) or the crosslinking agent cis-diamminedichloroplatinum (cisDDP). To determine the relative contribution of NHEJ and homologous recombination (HR) in Drosophila, Lig4; Rad54 double-mutant flies were generated. Survival studies demonstrated that both HR and NHEJ have a major role in DSB repair. The synergistic increase in sensitivity seen in the double mutant, in comparison with both single mutants, indicates that both pathways partially overlap. However, during the very first hours after fertilization NHEJ has a minor role in DSB repair after exposure to ionizing radiation. Throughout the first stages of embryogenesis of the fly, HR is the predominant pathway in DSB repair. At late stages of development NHEJ also becomes less important. The residual survival of double mutants after irradiation strongly suggests the existence of a third pathway for the repair of DSBs in Drosophila.

Original languageEnglish
Pages (from-to)1929-1941
Number of pages13
JournalGenetics
Volume165
Issue number4
Publication statusPublished - Dec 2003

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'The Drosophila melanogaster DNA Ligase IV Gene Plays a Crucial Role in the Repair of Radiation-Induced DNA Double-Strand Breaks and Acts Synergistically with Rad54'. Together they form a unique fingerprint.

  • Cite this

    Gorski, M. M., Eeken, J. C. J., De Jong, A. W. M., Klink, I., Loos, M., Romeijn, R. J., Van Veen, B. L., Mullenders, L. H., Ferro, W., & Pastink, A. (2003). The Drosophila melanogaster DNA Ligase IV Gene Plays a Crucial Role in the Repair of Radiation-Induced DNA Double-Strand Breaks and Acts Synergistically with Rad54. Genetics, 165(4), 1929-1941.