TATA BOX BINDING

PROTEINS

Bhaskar Ganguly
Ph.D., M.V.Sc., B.V.Sc. & A.H.

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 proteinDNA 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.

Role in Detection of DNA Damage

(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.

Thank You