Bhaskar GangulyPh.D., M.V.Sc., B.V.Sc. & A.H.

TATA BOX BINDING PROTEINS

STRUCTURE

• TBP is a saddle-shaped molecule, the binding of which to TATA-box DNA establishes an extensive hydrophobic protein-DNA interface of exceptional stability, thus, providing the protein-DNA platform required for assembly of a functional PIC.

• TATA binding protein (TBP) consists of two domains, an amino (N)-terminal domain that is species specific and a conserved carboxy C-terminal domain.

Structure…

• The conserved core domain directly contacts the TATA box of promoters; recognizes the TATA box sequence located 30 bp upstream from the transcription start site.

• Several homologues are known; the species specific N-terminal domain may be absent or entirely dissimilar.

HOMOLOGUES• TBP-like protein (TLP, TRF2 or TLF)– TLP regulates transcription by sequestering essential

factors, preventing their utilization in initiation complexes containing TBP

– TLP regulates transcription of a subset of genes required for cell proliferation

• TBP2 (TBPL2, TRF3)– The normal complement of TBP-associated factors is

not present in the complex associated with TBP2– Binds TATA box and mediates RNA polymerase (RNAP)

II transcription– Necessary for the embryonic development

Homologues…

• TRF-1– TBP homologue identified only in Drosophila

melanogaster– Capable of both sequence specific DNA binding and

transcriptional activation– Some developmental genes in Drosophila require TRF-

1 for transcription; in adult flies, however, TRF-1 is largely restricted to neuronal and testicular tissues

– A general transcription factor for RNAP III, but at different promoters, different times, and in different tissues than TBP

Role in Detection of DNA Damage

• Many viruses, carcinogens and anti-tumor agents structurally modify DNA, often at specific DNA sequences.

• Following DNA damage, cell cycle is arrested in G2/M and G1 phases and a decrease in the rate of transcription.

• A transcriptionally connected sub-pathway of DNA repair, called Nucleotide Excision Repair (NER) operates in which lesions in transcribed genes are preferentially repaired.

• The multi-protein complex TFIIH, essential for protein-encoding gene transcription, is also fundamental for NER.

• (TBP)-TFIID also interacts with damaged DNA.• Only specific damage leads to significant

inhibition of RNA polymerase II (RNA Pol II) transcription, although almost all damaged DNAs tested so far are repaired by the NER machinery.

• Inhibition of transcription is due to selective sequestration of TBP by damaged DNA.

• TBP recognizes selectively kinked DNA structure. Only some of the damaged DNAs which are repaired by the NER machinery are recognized by TBP-TFIID.

Role in Detection of DNA Damage…

• Sequestration of TBP reduces the pool of TFIID available for class II promoter transcription.

• Another possible consequence of the binding of TBP to lesions is the prevention of recognition of these lesions by DNA repair enzymes following binding with TBP.

Role in Detection of DNA Damage…

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