Diagram of sos repair mechanism pdf the TC-NER and GG-NER pathways. The two pathways differ only in initial DNA damage recognition. Recognition of the damage leads to removal of a short single-stranded DNA segment that contains the lesion.
The two subpathways differ in how they recognize DNA damage but they share the same process for lesion incision, repair, and ligation. The importance of NER is evidenced by the severe human diseases that result from in-born genetic mutations of NER proteins. There are 9 major proteins involved in NER in mammalian cells. Three different sets of proteins are involved in recognizing DNA damage for each subpathway. After damage recognition, the three subpathways converge for the steps of dual incision, repair, and ligation. Schematic depicts binding of proteins involved with GG-NER.
Global genomic NER repairs damage in both transcribed and untranscribed DNA strands in active and inactive genes throughout the genome. This process is not dependent on transcription. Additionally, XPA performs a function in damage recognition that is as yet poorly defined. Upon identification of a damaged site, subsequent repair proteins are then recruited to the damaged DNA to verify presence of DNA damage, excise the damaged DNA surrounding the lesion then fill in the repair patch. Schematic depicts binding of proteins involved with TC-NER. NER efficiency between transcriptionally silent and transcriptionally active regions of the genome.
For many types of lesions, NER repairs the transcribed strands of transcriptionally active genes faster than it repairs nontranscribed strands and transcriptionally silent DNA. TC-NER and GG-NER differ only in the initial steps of DNA damage recognition. The principal difference between TC-NER and GG-NER is that TC-NER does not require XPC or DDB proteins for distortion recognition in mammalian cells. DNA: the blocked RNA polymerase serves as a damage recognition signal, which replaces the need for the distortion recognition properties of the XPC-RAD23B and DDB complexes. DNA damage instead of XPC-Rad23B. Other repair mechanisms are possible but less accurate and efficient. TC-NER initiates when RNA polymerase stalls at a lesion in DNA, whereupon protein complexes help move the polymerase backwards.
TFIIH but then dissociate in an ATP-dependent manner and become bound to RPA. Inhibition of gap filling DNA synthesis and ligation results in an accumulation of RPA-bound sedDNAs in the cell. These two proteins are present prior to TFIIH binding since they are involved with verifying DNA damage. They may also protect single-stranded DNA. After verification, the 5′ side incision is made and DNA repair begins before the 3′ side incision.