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 comprised 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 Pol II transcription can occur in the absence of TFIID. TFTC containing the GCN5 acetyltransferase acetylates histone H3 in a nucleosomal context. We have identified a 130 kDa subunit of TFTC (SAP130) that shares homology with the large subunit of UV-damaged DNA-binding factor. TFTC preferentially binds UV-irradiated DNA, UV-damaged DNA inhibits TFTC-mediated Pol II transcription 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 results suggest that the access of DNA repair machinery to lesions within chromatin may be facilitated by TFTC via covalent modification of chromatin. Thus, our experiments reveal a molecular link between DNA damage recognition and chromatin modification.
Brand
M
M
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Department of 'Transcriptional and post-transcriptional control of gene regulation', CNRS/INSERM/ULP, BP 163, 67404 Illkirch Cedex, CU de Strasbourg.
Moggs
J G
JG
Oulad-Abdelghani
M
M
Lejeune
F
F
Dilworth
F J
FJ
Stevenin
J
J
Almouzni
G
G
Tora
L
L
D000107:Acetylation; D000595:Amino Acid Sequence; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism*; D013698:Templates, Genetic; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein
D004268:DNA-Binding Proteins; D006657:Histones; D009707:Nucleosomes; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C486349:SF3B3 protein, human; C491799:Sf3b1 protein, mouse; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein