Fig. 7
From: DNA damage sensitivity of SWI/SNF-deficient cells depends on TFIIH subunit p62/GTF2H1
Low GTF2H1 expression as a predictive marker for DNA damage hypersensitive SWI/SNF cancers. BRM- and BRG1-containing SWI/SNF complexes promote the expression of the GTF2H1 gene, a subunit of the TFIIH complex. In BRM- and BRG1-wild-type cells, normal expression of GTF2H1 allows the assembly of stable and functional TFIIH complexes, proficient in transcription and NER. When BRM or BRG1 are deficient, expression of GTF2H1 is lower, limiting the assembly of functional TFIIH complexes. As a consequence, transcription levels and NER capacity are lower, and cells become more sensitive to DNA damaging agents like UV and chemotherapeutic platinum drugs. Therefore, low GTF2H1 levels can likely be used as a marker to identify SWI/SNF cancers with increased sensitivity to chemotherapeutic drugs. However, cells with permanent loss of either BRM or BRG1 subunit can also adapt and restore the expression of GTF2H1, thus presenting normal transcription and NER activity. The mechanism underlying this adaption response is currently unknown, but if elucidated could be therapeutically exploited to specifically target SWI/SNF cancers with restored GTF2H1 expression, leaving surrounding non-tumor tissues intact
