Translesion DNA synthesis

The Interaction of Replication Forks with DNA Damage Can Lead to Error-Prone Translesion DNA Synthesis... 

At a stalled bacterial replication fork, there are two avenues for repair. In the absence of a second strand, the information required for accurate repair must come from a separate, homologous chromosome. The repair system thus involves homologous genetic recombination. This re combinational DNA repair is considered in detail in Section 25.3. Under some conditions, a second repair pathway, error-prone translesion DNA synthesis (often abbreviated TLS), becomes available. When this pathway is active, DNA repair becomes significantly less accurate and a high mutation rate can result. In bacteria, error-prone translesion DNA synthesis is part of a cellular stress response to extensive DNA damage known, appropriately enough, as the SOS response. Some SOS proteins, such as the UvrA and UvrB proteins already described (Table 25-6), are normally... 

In bacteria, error-prone translesion DNA synthesis, involving TLS DNA polymerases, occurs in response to very heavy DNA damage. In eukaryotes, similar polymerases have specialized roles in DNA repair that minimize the introduction of mutations. 

DNA glycosylases 971 AP site 971 AP endonucleases 972 DNA photolyases 974 recombinational DNA repair 976 error-prone translesion DNA synthesis 976 SOS response 976 homologous genetic recombination 978... 

However, much data has been accumulated in recent years indicating that the replication machinery can elongate past cisplatin-DNA lesions in a mutagenic way [15], Intervention of specific DNA polymerases and protein-protein interactions between replicative enzymes and DNA damage-recognition proteins may lead to occasional translesion DNA synthesis. This translesion synthesis can occur in an error-prone fashion, leading to indue-... 

Friedberg EC, Lehmann AR, Fuchs RP. Trading places how do DNA polymerases switch during translesion DNA synthesis Mol. Cell 2005 18 499-505. 

Shachar, S., Ziv, O., Avkin, S., Adar, S., Wittschieben, J., Reissner, T., Chaney, S., Friedberg, E.C., Wang, Z., Carell, T., Geadntov, N., and Livneh, Z. (2009) Two-polymerase mechanisms didate error-free and error-prone translesion DNA synthesis in mammals. EMBO J., 28, 383-393. 

What a difference a decade makes insights into translesion DNA synthesis. Proc. Natl. Acad. Sci. USA, 104,15591-15598. 

Devadoss, B., Lee, I., and Berdis, A.J. (2008) Enhancing the A-rule of translesion DNA synthesis promuta-genic DNA synthesis using modified nucleoside triphosphates. Biochemistry, 47, 8253-8260. 

Meneni, S.R., Liang, F., and Cho, B.P. (2007) Examination of the long-range effects of aminofluorene-induced conformational heterogeneity and its relevance to the mechanisms of translesion DNA synthesis. J. Mol. Biol., 366,1387-1400. 

Zahn, K.E., Belrhali, H Wallace, S.S., and Doublie, S. (2007) Caught bending the A-rule crystal structures of translesion DNA synthesis with a non-natural nucleotide. Biochemistry, 46, 10551-10561. 

Stafford, J.B., Eoff R.L., Kozekova, A., Rizzo, C.J., Guengerich, F.P., and Mamett, L.J. (2009) Translesion DNA synthesis by human DNA polymerase r on templates containing a pyrimido-purinone deoxyguanosine adduct, 3-(2 -deoxy- 3-D-erytJtro-pentofuranosyl) pyrimido-[l,2- ]purin-10(3H) one. Biochemistry, 48, 471-480. 

Avkin, S., Goldsmith, M., Velasco-Miguel, S., Geacintov, N., Friedberg, E.C., and Livneh, Z. (2004) Quantitative analysis of translesion DNA synthesis... 

Insight into the Molecular Mechanism of Translesion DNA Synthesis in Human Cells using Probes with Chemically Defined DNA Lesions... 

Hendel, A., Ziv, O., Gueranger, Q., Geacintov, N., and Iivneh, Z. (2008) Reduced fidelity and increased efficiency of translesion DNA synthesis across a TT cyclobutane pyrimidine dimer, but not... 

T., Geadntov, N., and Iivneh, Z. (2009) Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals. EMBO ]., 28, 383-393. 

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