DNA damage response system

Cadmium salts do not cause DNA damage in cell extracts or with isolated DNA [14] but rather interact with proteins therefore, the genotoxicity of cadmium is likely due to indirect mechanisms. Predominantly the induction of oxidative stress and interactions with the DNA damage response systems may be relevant in cadmium-induced genotoxicity. 

Kaplun, L., et al.. Functions of the DNA damage response pathway target Ho endonuclease of yeast for degradation via the ubiquitin-26S proteasome system. Proc Natl Acad Scl USA, 2000, 97(18), 10077-82. 

We begin with an overview of the origins of DNA damage, followed by summaries of the relationships between DNA lesions and disease, and a brief overview of cellular DNA damage response (DDR) systems, and conclude with a brief description of the specific topics covered in this book and how they relate to the field overall. 

Escherichia coli K12 TGI strain was used as a recipient for transformation. At studying of SOS-system activity the recombinant bioluminescent strain of Escherichia coli recA lux containing plasmid-borne fusions of the recA promoter-operator region to the Photorhabdus luminescens ZM 1 lux genes (GosNlIgenetika, Russia) was used. Increase of their luminescence in the presence of DNA damage factors [Rosen et al., 2000], were shown previously. Investigation of the luminescent response of this strain to UV radiation allows quantitatively estimate in a real time a SOS-system induction. 

The SOS response is an inducible DNA-repair system that allows bacteria to survive rapid increases in DNA damage. Two proteins play a key role in... 

The chemistry of DNA damage is diverse and complex. The cellular response to this damage includes a wide range of enzymatic systems that catalyze some of the most interesting chemical transformations in DNA metabolism. We first examine the effects of alterations in DNA sequence and then consider specific repair systems. 

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... 

There is a vast literature on the response of cellular systems, from bacteria to mammalian cells, but also animal and even clinical studies. In the present context, the emphasis will be on mechanistic details concerning the free-radical aspects. The most important late effects, notably the processing of DNA damage by the repair enzymes cannot be dealt with here. 

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