論文 - 詳細
| RRC ID | 45885 |
|---|---|
| 著者 | Wolters S, Ermolaeva MA, Bickel JS, Fingerhut JM, Khanikar J, Chan RC, Schumacher B. |
| タイトル | Loss of Caenorhabditis elegans BRCA1 promotes genome stability during replication in smc-5 mutants. |
| ジャーナル | Genetics |
| Abstract |
DNA damage by ultraviolet (UV) light poses a risk for mutagenesis and a potential hindrance for cell cycle progression. Cells cope with UV-induced DNA damage through two general strategies to repair the damaged nucleotides and to promote cell cycle progression in the presence of UV-damaged DNA. Defining the genetic pathways and understanding how they function together to enable effective tolerance to UV remains an important area of research. The structural maintenance of chromosomes (SMC) proteins form distinct complexes that maintain genome stability during chromosome segregation, homologous recombination, and DNA replication. Using a forward genetic screen, we identified two alleles of smc-5 that exacerbate UV sensitivity in Caenorhabditis elegans. Germ cells of smc-5-defective animals show reduced proliferation, sensitivity to perturbed replication, chromatin bridge formation, and accumulation of RAD-51 foci that indicate the activation of homologous recombination at DNA double-strand breaks. Mutations in the translesion synthesis polymerase polh-1 act synergistically with smc-5 mutations in provoking genome instability after UV-induced DNA damage. In contrast, the DNA damage accumulation and sensitivity of smc-5 mutant strains to replication impediments are suppressed by mutations in the C. elegans BRCA1/BARD1 homologs, brc-1 and brd-1. We propose that SMC-5/6 promotes replication fork stability and facilitates recombination-dependent repair when the BRC-1/BRD-1 complex initiates homologous recombination at stalled replication forks. Our data suggest that BRC-1/BRD-1 can both promote and antagonize genome stability depending on whether homologous recombination is initiated during DNA double-strand break repair or during replication stalling. |
| 巻・号 | 196(4) |
| ページ | 985-99 |
| 公開日 | 2014-4-1 |
| DOI | 10.1534/genetics.113.158295 |
| PII | genetics.113.158295 |
| PMID | 24424777 |
| PMC | PMC3982690 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism DNA Damage DNA Replication / radiation effects DNA, Helminth Genome, Helminth Genomic Instability* / radiation effects Germ Cells / metabolism Mutation Rad51 Recombinase / metabolism Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* |
| IF | 4.015 |
| 引用数 | 19 |
| WOS 分野 | GENETICS & HEREDITY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3886 tm1145 |