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. 2024 Apr 25;15:3490. doi: 10.1038/s41467-024-47935-9

Fig. 5. Prolonged TFIIH-DNA damage binding due to TC-NER activity impairs neuron functionality.

Fig. 5

Fraction of dye filling animals 72 h after increasing UV dose for (A) wild-type, xpc-1, xpf-1, and xpf-1;xpc-1, B wild-type, csb-1, xpf-1 and xpf-1;csb-1, C wild-type, xpc-1, csb-1, xpf-1, xpc-1;csb-1 and xpf-1;xpc-1;csb-1. Mean with SEM of two (xpf-1;xpc-1;csb-1) or three independent experiments. n (left to right)= (A) 75, 86, 63, 66, 81, 73, 51, 69, 73, 74, 35, 55, 75, 77, 28, 65, B 77, 70, 69, 67, 54, 74, 48, 68, 71, 78, 33, 50, 84, 67, 36 and 42, (C) 65, 59, 64, 39, 60, 32, 56, 68, 54, 30, 42, 19, 57, 63, 45, 37, 17, 61, 52, 46, 57, 19, 36, 13. D L1 larvae survival assay after 24 h of increasing dose illudin S in wild-type, xpf-1, xpa-1 and xpa;xpf-1. Mean with SEM of three independent experiments. n (left to right)= WT:900, 900, 900, 618, 427, 814, 606; xpa-1:900, 855, 876, 750, 713, 963, 900; xpf-1:957, 732, 858, 670, 467, 725, 725; xpa-1;xpf-1:900, 900, 606, 401, 432, 389, 900. (E) Fraction of dye filling animals 72 h after 24 h treatment with illudin S for wild-type, xpf-1 and xpf-1;gtf-2H5. Mean with SEM of four independent experiments. n (left to right)= wild-type:72, 59, 48; xpf-1:68, 60, 26; xpf-1;gtf-2H5:66, 68, 39. Numbers in (A)–(E) represent p-values (ANOVA corrected for multiple comparisons), comparing the double or triple mutant to xpf-1. F Model showing difference in NER mechanism between cells with normal NER, completely lacking XPF or XPG function or lacking XPA or TTDA function. In cells with normal NER, both DNA damage and NER incision complex are removed and cells function normally. In cells completely lacking XPF or XPG, DNA damage is not removed and TFIIH stalls persistently to non-excised DNA damage, contributing to cellular dysfunction, senescence and severe NER disease. In cells lacking XPA or TTDA, DNA damage is not removed, but TFIIH does not stably bind to DNA damage, causing less cell dysfunction and a milder, or different, NER disease. Source data are provided as a Source Data file.