Transcription-repair coupling factor
Each cell has a series of special enzymes to correct the errors in DNA sequences. This process, called DNA repair protects genetic information against environmental damages and replication errors, thus restoring the original DNA sequence. Although we do not usually recognize so, our DNA is damaged constantly every day. In human cells, thousands of DNA sites are damaged every day by heat, metabolic accidents, radiation of various sorts and exposure to substances in the environment. If DNA damages were not repaired, people would become diseases such as colon cancers and skin cancers, but in reality, almost all are repaired by remarkably efficient mechanisms. Only less than one of a thousand results in a permanent mutation. Furthermore, DNA damages in active regions of the genome are preferentially repaired compared to those in inactive regions. This system is called transcription-coupled DNA repair, triggered by RNA polymerase stalled at lesions in the damaged DNA strands.
The structure shown here is a transcription-coupled DNA repair protein (1148-amino acid residues) working in Escherichia coli. It is known to work for removal of a stalled RNA polymerase covering the damaged DNA, and to stimulate DNA repair by recruitment of endonucleases that break down the damaged DNA strand.
It is composed of compact arrangement of eight domains. Each domain is thought to have distinct abilities such as translocation of DNA, recognition of damaged DNA by binding there, and interaction with RNA polymerase. Inside the translocation module, an ATPase module is located. All these domains are connected by flexible linkers, suggesting during real functional cycle, these domains are rearranged by large-scale conformational changes.
Protein Data Bank (PDB)
Deaconescu, A.M. Chambers, A.L. Smith, A.J. Nickels, B.E. Hochschild, A. Savery, N.J. Darst, S.A.; "Structural basis for bacterial transcription-coupled DNA repair."; Cell (Cambridge,Mass.); (2006) 124:507-520 PubMed:16469698.
author: Sachiyo Nomura