Reference - Detail
| RRC ID | 83970 |
|---|---|
| Author | Muniesa-Vargas A, Davó-Martínez C, Ribeiro-Silva C, van der Woude M, Thijssen KL, Haspels B, Häckes D, Kaynak ÜU, Kanaar R, Marteijn JA, Theil AF, Kuijten MMP, Vermeulen W, Lans H. |
| Title | Persistent TFIIH binding to non-excised DNA damage causes cell and developmental failure. |
| Journal | Nat Commun |
| Abstract |
Congenital nucleotide excision repair (NER) deficiency gives rise to several cancer-prone and/or progeroid disorders. It is not understood how defects in the same DNA repair pathway cause different disease features and severity. Here, we show that the absence of functional ERCC1-XPF or XPG endonucleases leads to stable and prolonged binding of the transcription/DNA repair factor TFIIH to DNA damage, which correlates with disease severity and induces senescence features in human cells. In vivo, in C. elegans, this prolonged TFIIH binding to non-excised DNA damage causes developmental arrest and neuronal dysfunction, in a manner dependent on transcription-coupled NER. NER factors XPA and TTDA both promote stable TFIIH DNA binding and their depletion therefore suppresses these severe phenotypical consequences. These results identify stalled NER intermediates as pathogenic to cell functionality and organismal development, which can in part explain why mutations in XPF or XPG cause different disease features than mutations in XPA or TTDA. |
| Volume | 15(1) |
| Pages | 3490 |
| Published | 2024-4-25 |
| DOI | 10.1038/s41467-024-47935-9 |
| PII | 10.1038/s41467-024-47935-9 |
| PMID | 38664429 |
| PMC | PMC11045817 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism DNA Damage* DNA Repair* DNA-Binding Proteins* / genetics DNA-Binding Proteins* / metabolism Endonucleases* / genetics Endonucleases* / metabolism Humans Mutation Nuclear Proteins / genetics Nuclear Proteins / metabolism Protein Binding Transcription Factor TFIIH* / genetics Transcription Factor TFIIH* / metabolism Transcription Factors / genetics Transcription Factors / metabolism Xeroderma Pigmentosum Group A Protein / genetics Xeroderma Pigmentosum Group A Protein / metabolism |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm6360 tm2842 tm3886 tm1682 tm1670 |