DNA Damage Tolerance

DNA repair is the major cellular defense system against DNA damage, which physically removes the lesions from DNA. Cell cycle checkpoint control empowers the repair system with better efficiency in that the cell cycle is temporarily halted to allow more time for DNA repair. In multicell organisms, apoptosis is additionally employed to remove excessively damaged cells. Nevertheless, these cellular defense 

4 Error-Prone Translesion Synthesis Is the Major Mechanism of Base Damage-Induced Mutagenesis 

Error-free versus error-prone is a relative description for the accuracy of translesion synthesis. Sometimes, it may not be obvious to distinguish between error-free and error-prone based on in vitro biochemical analysis of a polymerase in response to a specific lesion. The ultimate distinction between these two modes of translesion synthesis in cells can be made through genetic analysis. If the polymerase activity suppresses the lesion-induced mutagenesis, then, it is error-free. If the polymerase activity promotes the lesion-induced mutagenesis, then, it is error-prone. 

5 Base Damage-Induced Mutagenesis Is A Major Component of the SOS Response in E. coli 

coli translesion polymerases, DNA polymerases II, IV, and V, are under the control of the SOS system. While DNA polymerases II, IV are involved in translesion synthesis of a few selected types of lesions, DNA polymerase V is the 

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UBC13 153 Rad5 [73] Heterodimerizes with Mms2 (UEV) [72] DNA-damage tolerance [72] via polyubiquiti-nation of PCNA [65] (non-proteolytic function)... 

Sutton, M.D., Smith, B.T., Godoy, V.G., Walker, G.C. (2000) The SOS response recent insights into umuDC-dependent mutagenesis and DNA damage tolerance. Annu. Rev. Genet. 34, 479-497. 

Figure 22.24. A molecular switch model for the control of the two pathways of DNA damage tolerance, template switching, and translesion synthesis. The PCNA processivity DNA clamp is shown as a homotrimer. Both SUMO-modification (S) and ubiquitination (U) occur at the K164 position of PCNA. [Adapted from Stelter, P., and Ulrich, H. D. Nature 425,188-191, 2003.]...

Figure 1. Schematic presentation of (A) DNA repair mechanisms 1. Photoreactivation also known as photoenzymatic repair, and 2. Nucleotide excision repair where the lesion damaged by exposure to UV-B is reversed (photoreactivation) or expelled (nucleotide excision repair) (B) DNA damage tolerance mechanisms 1. Dimer bypass and 2. Recombinational repair where replication proceeds around the lesion and the gap is filled in by adenine (dimer bypass) or a homologous sequence is inserted (recombinational repair).

A specialized set of DNA polymerases cooperate to successfully replicate the strand containing the damaged nucleotide (Chapters 13-17). However, this mechanism of DNA damage tolerance is error-prone, and the fidelity of translesion bypass in human cells depends on the DNA lesion and the polymerase [17]. The progress of RNA polymerases depends generally on the size and shape of the DNA adduct, the local DNA sequence (Chapter 17), and the structure of the active site of the RNA polymerase [72, 73]. 

The SOS response recent insights into umuDC-dependent mutagenesis and DNA damage tolerance. Annu. Rev. Genet. 34, 479-497. 

Simpson, L. J., and Sale, J. E. (2003). Revl is essential foe DNA damage tolerance and non-teplated immunogobulin gene mutation in a vertebrate cell line. EMBOJ. 22, 1654-1664. 

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