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Polycomb group (PcG) proteins establish and maintain genetic programs that regulate cell-fate decisions. Drosophila multi sex combs (mxc) was categorized as a PcG gene based on a classical Polycomb phenotype and genetic interactions; however, a mechanistic connection between Polycomb and Mxc has not been elucidated. Hypomorphic alleles of mxc are characterized by male and female sterility and ectopic sex combs. Mxc is an important regulator of histone synthesis, and we find that increased levels of the core histone H3 in mxc mutants result in replicative stress and a persistent DNA damage response (DDR). Germline loss, ectopic sex combs and the DDR are suppressed by reducing H3 in mxc mutants. Conversely, mxc phenotypes are enhanced when the DDR is abrogated. Importantly, replicative stress induced by hydroxyurea treatment recapitulated mxc germline phenotypes. These data reveal how persistent replicative stress affects gene expression, tissue homeostasis, and maintenance of cellular identity in vivo.
Pubmed ID: 24746823 RIS Download
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Biomaterial supply resource which collects, maintains, and distributes independent transgenic fly lines. Most of the 38,000 fly lines are RNAi lines, but VDRC also maintains a collection of enhancer-GAL4 driver lines. Nearly all lines are in duplicate. Users can search for the stocks or DNA constructs for the gene of interest by entering CG number, synonym, or Transformant ID.
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