論文 - 詳細
| RRC ID | 51548 |
|---|---|
| 著者 | León-Ortiz AM, Panier S, Sarek G, Vannier JB, Patel H, Campbell PJ, Boulton SJ. |
| タイトル | A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination. |
| ジャーナル | Mol Cell |
| Abstract |
Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. |
| 巻・号 | 69(2) |
| ページ | 292-305.e6 |
| 公開日 | 2018-1-18 |
| DOI | 10.1016/j.molcel.2017.12.014 |
| PII | S1097-2765(17)30966-8 |
| PMID | 29351848 |
| PMC | PMC5783719 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Helicases / genetics DNA Helicases / metabolism* DNA Mismatch Repair DNA Repair / genetics DNA Replication Genomic Instability / genetics Genomic Instability / physiology* Mutation RecQ Helicases / metabolism Recombination, Genetic / genetics |
| IF | 15.584 |
| 引用数 | 9 |
| 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 | 8 |
| 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 | tm1866 tm424 |