title: A role for the malignant brain tumour (MBT) domain protein LIN-61 in DNA double-strand break repair by homologous recombination.
abstract: Malignant brain tumour (MBT) domain proteins are transcriptional repressors that function within Polycomb complexes. Some MBT genes are tumour suppressors, but how they prevent tumourigenesis is unknown. The Caenorhabditis elegans MBT protein LIN-61 is a member of the synMuvB chromatin-remodelling proteins that control vulval development. Here we report a new role for LIN-61: it protects the genome by promoting homologous recombination (HR) for the repair of DNA double-strand breaks (DSBs). lin-61 mutants manifest numerous problems associated with defective HR in germ and somatic cells but remain proficient in meiotic recombination. They are hypersensitive to ionizing radiation and interstrand crosslinks but not UV light. Using a novel reporter system that monitors repair of a defined DSB in C. elegans somatic cells, we show that LIN-61 contributes to HR. The involvement of this MBT protein in HR raises the possibility that MBT-deficient tumours may also have defective DSB repair.
authors.affiliation: Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Johnson
authors.forename: Bennie B L G
authors.initials: BB
authors.lastname: Lemmens
authors.forename: Marcel
authors.initials: M
authors.lastname: Tijsterman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D042822:Genomic Instability / Q000235:genetics; D005854:Germ Cells / Q000378:metabolism; D059765:Homologous Recombination / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D009154:Mutation; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D014466:Ultraviolet Rays
chemical_list: D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; C559591:LIN-61 protein, C elegans