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The role of MOF in the ionizing radiation response is conserved in Drosophila melanogaster

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Abstract

In Drosophila, males absent on the first (MOF) acetylates histone H4 at lysine 16 (H4K16ac). This acetylation mark is highly enriched on the male X chromosome and is required for dosage compensation in Drosophila but not utilized for such in mammals. Recently, we and others reported that mammalian MOF, through H4K16ac, has a critical role at multiple stages in the DNA damage response (DDR) and double-strand break repair pathways. The goal of this study was to test whether mof is similarly required for the response to ionizing radiation (IR) in Drosophila. We report that Drosophila mof mutations in males and females, as well as mof knockdown in SL-2 cells, reduce post-irradiation survival. MOF depletion in SL-2 cells also results in an elevated frequency of metaphases with chromosomal aberrations, suggesting that MOF is involved in DDR. Mutation in Drosophila mof also results in a defective mitotic checkpoint, enhanced apoptosis, and a defective p53 response post-irradiation. In addition, IR exposure enhanced H4K16ac levels in Drosophila as it also does in mammals. These results are the first to demonstrate a requirement for MOF in the whole animal IR response and suggest that the role of MOF in the response to IR is conserved between Drosophila and mammals.

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Acknowledgments

Thanks are due to Edwin Smith and Peter Becker for providing regents and valuable suggestions and to Fan Zhang with help in irradiating mof 3 /mof 6 flies. We also thank members of Pandita laboratory for helpful discussions and suggestions.

Funding

This work was supported by NIH NCI grants R01CA123232, R01CA129537, RO1CA154320, and R13CA130756 (TKP); NSF grants MCB 0131414 and MCB 0615831 (JCE); NIGMS grant RO115691 (JCL); and Senior Wellcome Trust fellowship grants, GRA070065MA (UB) and (GRA076395AIA) (MPB).

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Authors and Affiliations

  1. Indian Institute of Chemical Technology, Hyderabad, AP, 500007, India

    Manika P. Bhadra & Anita Krishnan

  2. Center for Cellular and Molecular Biology, Hyderabad, AP, 500007, India

    Manika P. Bhadra, Sreerangam NCVL Pushpavallipvalli, Arpita Sarkar, Indira Bag, Anita Krishnan & Utpal Bhadra

  3. UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Nobuo Horikoshi, Rakesh Kumar, Raj K. Pandita, Mayank Singh & Tej K. Pandita

  4. Washington University School of Medicine, St Louis, MO, USA

    Rakesh Kumar, Qin Yang & Tej K. Pandita

  5. Emory University, Atlanta, GA, 30322, USA

    John C. Lucchesi

  6. Saint Louis University School of Medicine, St Louis, MO, 63104, USA

    Joel C. Eissenberg

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  1. Manika P. Bhadra
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  2. Nobuo Horikoshi
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  9. Qin Yang
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  10. Raj K. Pandita
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  12. Utpal Bhadra
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  14. Tej K. Pandita
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Correspondence to Tej K. Pandita.

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Bhadra, M.P., Horikoshi, N., Pushpavallipvalli, S.N. et al. The role of MOF in the ionizing radiation response is conserved in Drosophila melanogaster . Chromosoma 121, 79–90 (2012). https://doi.org/10.1007/s00412-011-0344-7

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