RRC ID 46373
Author Johnson NM, Lemmens BB, Tijsterman M.
Title A role for the malignant brain tumour (MBT) domain protein LIN-61 in DNA double-strand break repair by homologous recombination.
Journal PLoS Genet
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.
Volume 9(3)
Pages e1003339
Published 2013-1-1
DOI 10.1371/journal.pgen.1003339
PMID 23505385
PMC PMC3591299
MeSH Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Cell Transformation, Neoplastic* / genetics Cell Transformation, Neoplastic* / radiation effects Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone* / genetics Chromosomal Proteins, Non-Histone* / metabolism DNA Breaks, Double-Stranded / radiation effects DNA Repair* / genetics DNA Repair* / radiation effects Genomic Instability / genetics Germ Cells / metabolism Homologous Recombination / genetics Homologous Recombination / radiation effects Humans Mutation Radiation Tolerance / genetics Radiation, Ionizing Ultraviolet Rays
IF 5.175
Times Cited 11
C.elegans tm2649 tm1866 tm1145 tm649