Direct Reversal of DNA Alkylation Damage

Department of Chemistry, University of Chicago, Chicago, Illinois, United States
Chemical Reviews (Impact Factor: 45.66). 03/2006; 106(2):215-32. DOI: 10.1021/cr0404702
Source: PubMed

ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Repair and defence of genome integrity from endogenous and environmental hazard is a primary need for all organisms. Natural selection has driven the evolution of multiple cell pathways to deal with different DNA damaging agents. Failure of such processes can hamper cell functions and induce inheritable mutations, which in humans may cause cancerogenicity or certain genetic syndromes, and ultimately cell death. A special case is that of hyperthermophilic bacteria and archaea, flourishing at temperatures higher than 80 °C, conditions that favor genome instability and thus call for specific, highly efficient or peculiar mechanisms to keep their genome intact and functional. Over the last few years, numerous studies have been performed on the activity, function, regulation, physical and functional interaction of enzymes and proteins from hyperthermophilic microorganisms that are able to bind, repair, bypass damaged DNA, or modify its structure or conformation. The present review is focused on two enzymes that act on DNA catalyzing unique reactions: reverse gyrase and DNA alkyltransferase. Although both enzymes belong to evolutionary highly conserved protein families present in organisms of the three domains (Eucarya, Bacteria and Archaea), recently characterized members from hyperthermophilic archaea show both common and peculiar features.
    Extremophiles 08/2014; 18(5). DOI:10.1007/s00792-014-0662-9 · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The O6-alkylguanine DNA alkyltransferase (AGT) is a highly conserved protein responsible for direct repair of alkylated guanine and to a lesser degree thymine bases. While specific DNA lesion-bound complexes in crystal structures consist of monomeric AGT, several solution studies have suggested that cooperative DNA binding plays a role in the physiological activities of AGT. Cooperative AGT–DNA complexes have been described by theoretical models, which can be tested by atomic force microscopy (AFM). Direct access to structural features of AGT–DNA complexes at the single molecule level by AFM imaging revealed non-specifically bound, cooperative complexes with limited cluster length. Implications of cooperative binding in AGT–DNA interactions are discussed.
    DNA repair 08/2014; 20. DOI:10.1016/j.dnarep.2014.01.006 · 3.36 Impact Factor
  • Source
    Selected Topics in DNA Repair, 10/2011; , ISBN: 978-953-307-606-5


Available from