DNA repair proteins

There has been much recent interest in the role of zinc in activating cysteine residues to nucleophilic attack.542-545 Alkyl group transfer to coordinated cysteine residues occurs in a number of zinc proteins, such as Ada (the E. coli DNA repair protein) and the cobala-... 

Overall, it can be envisioned that the Py-G group 47 represents an important label for the time-resolved studies of DNA dynamics and stacking interaction [123] and could be applied especially for assays in which conformational changes or base-flipping processes are essential in observation, such as in the investigation of DNA-protein complexes with DNA repair proteins. 

Figure 2 Double-stranded oligonucleotide photoprobes that simulate modified DNA and intended to cross-link to DNA-binding proteins. (A) Probe modeling interstrand cross-linking by cisplatin Source From Ref. [63], with permission from the American Chemical Society via the Rightslink service (license number 2458870278307 granted June 30, 2010). The benzophenone probe prior to reaction with DNA is shown in the lower part of the panel. (B) Photoaffinity probe for bacterial DNA repair proteins. TT is a simulated thymine dimer intended to be recognized as a site of damage in DNA, and T (two instances) is the diazirine thymine derivative T Source From Ref. [64], with permission from Wiley.

Figure 12.8 Some other active-site coordination motifs in mononuclear zinc enzymes from left to right bacteriophage T7 lysozyme, 5-aminolaevulinate dehydratase, Ada DNA repair protein. (Reprinted with permission from Parkin, 2004. Copyright (2004) American Chemical Society.)...

An in-depth study of DNA repair systems (Aravind et al., 1999a) has concluded that few, if any, repair proteins occur with identical collinear domain arrangements in all three kingdoms of life. Approximately 10 enzyme families of adenosine triphosphatases (ATPases), photolyases, helicases, and nucleases were identified that are all likely to have been present in the cenancestor. These enzymatic domains are accompanied in DNA repair proteins by numerous regulatory domains. This indicates that the domain architectures of these proteins are labile, with incremental addition and/or subtraction of domains to conserved cores to be a common phenomenon except in the most closely related species. 

ScHAUBER, C., and Madura, K., The DNA repair protein rad23 is a negative regulator of multi-ubiquitin chain assembly, Nat. Cell Biol., 2000, 2, 601. 

How does PARP-Fs role as a nucleosome-binding protein and modulator of chromatin structure, which is evident under normal physiological conditions, impact PARP-1-dependent DNA repair, cell death, and inflammatory response pathways, which occur under pathophysiological conditions A number of different scenarios are possible. For example, PARP-l s chromatin-dependent activities may be critical for its function as a DNA repair protein, since the repair of genomic DNA must occur in the context of chromatin. In addition, nucleosome-stimulated autoPARylation may play a role in depleting cellular NAD+ pools in response to cellular stresses. Furthermore, PARP-Fs chromatin-dependent activities may help to regulate the expression of immune and inflammatory response genes. These possibilities will need to be examined in the future. 

Dery, U., Coulombe, Y, Rodrigue, A., Stasiak, A., Richard, S. and Masson, J.Y. (2008) A glycine-arginine domain in control of the human MREll DNA repair protein. Molecular and Cellular Biology, 28, 3058-3069. 

Fig. 1. Proteins in DNA repair pathways. DNA repair proteins are listed for each of the following pathways BER (Base Excision Repair), NER (Nucleotide Excision Repair), MMR (Mismatch Repair), HR (Homologous Recombination), and NHEJ (Nonhomologous End Joining). PARP1/2 and BRCA1/2 are relevant in BER and HR pathways, respectively.

QCPMG to study the nature of Mg -binding sites in a DNA repair protein. With such an approach, they showed the disordered nature of the single Mg " "-binding site to the protein, both in the presence and in the absence of DNA. 

Madhusudan S, Middleton MR. The emerging role of DNA repair proteins as predictive, prognostic and therapeutic targets in cancer. Cancer Treat Rev. 2005 31 603-617. 

Lorente de No R (1934) Studies on the structure of the cerebral cortex. II. Continuation of the study of the Ammonic system. J Psychol Neurol 46 113-177 Love S, Barber R, Wilcock GK (1998) Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man. Neuroreport 9 955-959 Love S, Barber R, Wilcock GK (1999) Neuronal accumulation of poly(ADP-ribose) after brain ischaemia. Neuropathol Appl Neurobiol 25 98-103 Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11 173-189 Magavi SS, Leavitt BR, Macklis JD (2000) Induction of neurogenesis in the neocortex of adult mice. Nature 405 951-955... 

Covalent attachment of the small molecule to the fusion protein is achieved by the unusual mechanism of the human DNA repair protein 06-alkylguanine-DNA alkyltransferase (hAGT), which irreversibly transfers the alkyl group from its substrate, 06-alkylguanine-DNA, to one of its cysteine residues (Figure 4.4.1A) [11],... 

Fransson, J. and C. A. Borrebaeck (2006). The nuclear DNA repair protein Ku70/80 is a tumor-associated antigen displaying rapid receptor mediated endocytosis. IntJ Cancer 119(10) 2492-2496. 

It can activate DNA repair proteins when DNA has sustained damage. 

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