RRC ID |
46373
|
著者 |
Johnson NM, Lemmens BB, Tijsterman M.
|
タイトル |
A role for the malignant brain tumour (MBT) domain protein LIN-61 in DNA double-strand break repair by homologous recombination.
|
ジャーナル |
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.
|
巻・号 |
9(3)
|
ページ |
e1003339
|
公開日 |
2013-1-1
|
DOI |
10.1371/journal.pgen.1003339
|
PII |
PGENETICS-D-12-01003
|
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
|
引用数 |
11
|
WOS 分野
|
GENETICS & HEREDITY
|
リソース情報 |
線虫 |
tm2649
tm1866
tm1145
tm649 |