論文 - 詳細
| RRC ID | 3535 |
|---|---|
| 著者 | Polanowska J, Martin JS, Garcia-Muse T, Petalcorin MI, Boulton SJ. |
| タイトル | A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA damage sites. |
| ジャーナル | EMBO J |
| Abstract |
The BRCA1 tumour suppressor and its heterodimeric partner BARD1 constitute an E3-ubiquitin (Ub) ligase and function in DNA repair by unknown mechanisms. We show here that the Caenorhabditis elegans BRCA1/BARD1 (CeBCD) complex possesses an E3-Ub ligase responsible for ubiquitylation at DNA damage sites following ionizing radiation (IR). The DNA damage checkpoint promotes the association of the CeBCD complex with E2-Ub conjugating enzyme, Ubc5(LET-70), leading to the formation of an active E3-Ub ligase on chromatin following IR. Correspondingly, defects in Ubc5(let-70) or the DNA damage checkpoint genes atl-1 or mre-11 abolish CeBCD-dependent ubiquitylation in vivo. Extending these findings to human cells reveals a requirement for UbcH5c, the MRN complex, gamma-H2AX and a co-dependence for ATM and ATR kinases for BRCA1-dependent ubiquitylation at DNA damage sites. Furthermore, we demonstrate that the DNA damage checkpoint promotes the association between BRCA1 and UbcH5c to form an active E3-Ub ligase on chromatin after IR. These data reveal that BRCA1-dependent ubiquitylation is activated at sites of DNA repair by the checkpoint as part of a conserved DNA damage response. |
| 巻・号 | 25(10) |
| ページ | 2178-88 |
| 公開日 | 2006-5-17 |
| DOI | 10.1038/sj.emboj.7601102 |
| PII | 7601102 |
| PMID | 16628214 |
| PMC | PMC1462971 |
| MeSH | Animals BRCA1 Protein / genetics BRCA1 Protein / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Line Chromatin / metabolism DNA Damage* DNA Repair Enzyme Activation Humans Multiprotein Complexes RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Rad51 Recombinase / genetics Rad51 Recombinase / metabolism Signal Transduction / physiology* Ubiquitin / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism |
| IF | 9.889 |
| 引用数 | 110 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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 | F1000Research |
| 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 | tm1145 tm853 |