Transcription-coupled repair
Encyclopedia
Transcription-coupled repair is a DNA repair
mechanism which operates in tandem with transcription
. The activity of TCR has been known for 20 years, but its mechanism of action is an area of current research. Failure of the transcription-coupled repair is the cause of Cockayne syndrome
, an extreme form of accelerated aging that is fatal early in life.
to instruct protein synthesis by RNA polymerase II
. When RNA polymerase finds a lesion in the DNA, like those caused by UV light it stops and the gene is not transcribed. TCR is associated with RNA polymerase II, and the stalled RNAP is the trigger for TCR both in prokaryotes and eukaryotes.
Researchers looked at the CSB protein, which is mutated in patients with Cockayne syndrome, and found that it is associated with XPG (another protein associated with the syndrome) and found that RNA polymerase II is stalled during transcription, XPG and CSB respond to the stalled transcription bubble. They then recruit transcription factor II H
and other proteins and protein complexes to remodel RNA polymerase, gain access to the bubble, and repair the lesion while leaving polymerase in place.
Other repair mechanisms are possible but less accurate and efficient.
TCR also exists in bacteria, and is mediated by the TRCF (Mfd) protein. TRCF is an SF2 ATPase that uses ATP hydrolysis to translocate on dsDNA upstream of the transcription bubble and forward translocate RNA Polymerase, thus initiating dissociation of the RNA Polymerase ternary elongation complex. TRCF also recruits the Uvr(A)BC nucleotide excision repair machinery by direct physical interaction with the UvrA subunit.
DNA repair
DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
mechanism which operates in tandem with transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
. The activity of TCR has been known for 20 years, but its mechanism of action is an area of current research. Failure of the transcription-coupled repair is the cause of Cockayne syndrome
Cockayne syndrome
Cockayne syndrome is a rare autosomal recessive, congenital disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight , and premature aging...
, an extreme form of accelerated aging that is fatal early in life.
Mechanism
Genes are copied from DNA to make messenger RNAMessenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
to instruct protein synthesis by RNA polymerase II
RNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
. When RNA polymerase finds a lesion in the DNA, like those caused by UV light it stops and the gene is not transcribed. TCR is associated with RNA polymerase II, and the stalled RNAP is the trigger for TCR both in prokaryotes and eukaryotes.
Researchers looked at the CSB protein, which is mutated in patients with Cockayne syndrome, and found that it is associated with XPG (another protein associated with the syndrome) and found that RNA polymerase II is stalled during transcription, XPG and CSB respond to the stalled transcription bubble. They then recruit transcription factor II H
General transcription factor
General transcription factors or basal transcription factors are protein transcription factors that have been shown to be important in the transcription of class II genes to mRNA templates...
and other proteins and protein complexes to remodel RNA polymerase, gain access to the bubble, and repair the lesion while leaving polymerase in place.
Other repair mechanisms are possible but less accurate and efficient.
TCR also exists in bacteria, and is mediated by the TRCF (Mfd) protein. TRCF is an SF2 ATPase that uses ATP hydrolysis to translocate on dsDNA upstream of the transcription bubble and forward translocate RNA Polymerase, thus initiating dissociation of the RNA Polymerase ternary elongation complex. TRCF also recruits the Uvr(A)BC nucleotide excision repair machinery by direct physical interaction with the UvrA subunit.