UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation

Initiation of transcription of protein-encoding genes by RNA polymerase II (Pol II) was thought to require transcription factor TFIID, a complex compr ised of the TATA box-binding protein (TBP) and TBP-associated factors (TAF( II)s). In the presence of TBP-free TAF(II) complex (TFTC), initiation of Po l II transcription can occur in the absence of TFIID, TFTC containing the G CN5 acetyltransferase acetylates histone H3 in a nucleosomal context. We ha ve identified a 130 kDa subunit of TFTC (SAP130) that shares homology with the large subunit of UV-damaged DNA-binding factor. TFTC preferentially bin ds UV-irradiated DNA, UV-damaged DNA inhibits TFTC-mediated Pol II transcri ption and TFTC is recruited in parallel with the nucleotide excision repair protein XP-A to UV-damaged DNA, TFTC preferentially acetylates histone H3 in nucleosomes assembled on UV-damaged DNA, In agreement with this, strong histone H3 acetylation occurs in intact cells after UV irradiation. These r esults suggest that the access of DNA repair machinery to lesions within ch romatin may be facilitated by TFTC via covalent modification of chromatin, Thus, our experiments reveal a molecular link between DNA damage recognitio n and chromatin modification.