論文 - 詳細
| RRC ID | 18151 |
|---|---|
| 著者 | Saito TT, Mohideen F, Meyer K, Harper JW, Colaiácovo MP. |
| タイトル | SLX-1 is required for maintaining genomic integrity and promoting meiotic noncrossovers in the Caenorhabditis elegans germline. |
| ジャーナル | PLoS Genet |
| Abstract |
Although the SLX4 complex, which includes structure-specific nucleases such as XPF, MUS81, and SLX1, plays important roles in the repair of several kinds of DNA damage, the function of SLX1 in the germline remains unknown. Here we characterized the endonuclease activities of the Caenorhabditis elegans SLX-1-HIM-18/SLX-4 complex co-purified from human 293T cells and determined SLX-1 germline function via analysis of slx-1(tm2644) mutants. SLX-1 shows a HIM-18/SLX-4-dependent endonuclease activity toward replication forks, 5'-flaps, and Holliday junctions. slx-1 mutants exhibit hypersensitivity to UV, nitrogen mustard, and camptothecin, but not gamma irradiation. Consistent with a role in DNA repair, recombination intermediates accumulate in both mitotic and meiotic germ cells in slx-1 mutants. Importantly, meiotic crossover distribution, but not crossover frequency, is altered on chromosomes in slx-1 mutants compared to wild type. This alteration is not due to changes in either the levels or distribution of double-strand breaks (DSBs) along chromosomes. We propose that SLX-1 is required for repair at stalled or collapsed replication forks, interstrand crosslink repair, and nucleotide excision repair during mitosis. Moreover, we hypothesize that SLX-1 regulates the crossover landscape during meiosis by acting as a noncrossover-promoting factor in a subset of DSBs. |
| 巻・号 | 8(8) |
| ページ | e1002888 |
| 公開日 | 2012-8-1 |
| DOI | 10.1371/journal.pgen.1002888 |
| PII | PGENETICS-D-12-00857 |
| PMID | 22927825 |
| PMC | PMC3426554 |
| MeSH | Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Cell Line DNA Damage / drug effects DNA Damage / radiation effects DNA Helicases / metabolism Deoxyribonucleases / metabolism* Endodeoxyribonucleases / metabolism Genome Genomic Instability* Humans Male Meiosis* |
| IF | 5.175 |
| 引用数 | 22 |
| 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
|
| 最多言及媒体 | |
| 各媒体での言及数の合計 | 1 |
| 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 | slx-1(tm2644) brc-2(tm1086) him-18(tm2181) |