例如:"lncRNA", "apoptosis", "WRKY"

RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment.

J Biol Chem. 2016 Apr 29;291(18):9396-410. Epub 2016 Feb 22
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
{{ author.authorName }}{{getOrganisationIndexOf(author)}} {{ author.authorName }}{{getOrganisationIndexOf(author)}}
+ et al

[No authors listed]

Author information
  • {{index+1}} {{ organisation }}

摘要


DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13∼ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}

基因功能


  • {{$index+1}}.{{ gene }}

图表


原始数据


 保存测序数据
Sample name
Organism Experiment title Sample type Library instrument Attributes
{{attr}}
{{ dataList.sampleTitle }}
{{ dataList.organism }} {{ dataList.expermentTitle }} {{ dataList.sampleType }} {{ dataList.libraryInstrument }} {{ showAttributeName(index,attr,dataList.attributes) }}

文献解读