Resolving DNA Repair

Abstract

Molecular Biology![Figure][1] DNA with bound repair proteins. CREDIT: BOAL ET AL., PROC. NATL. ACAD. SCI. U.S.A. 106 , 15237 (2009) Base excision repair (BER) enzymes involved in fixing damaged DNA have low specificity for their targets and occur in low numbers in cells. So how are DNA damage sites located on chromosomes with any efficiency? Boal et al. suggest that the key lies in DNA charge transport chemistry, so that repair proteins can signal to each other rapidly over long distances. The ordered stacking that occurs in DNA makes it an excellent medium for electron transport, and the process is very sensitive to the presence of mismatched bases. When a BER enzyme containing an [4Fe4S] cluster binds DNA it becomes oxidized. In the absence of damage, when a second protein binds, electron transfer will occur and the reduced member of the protein pair will diffuse away. However, if there is damage, both proteins remain bound and, fairly rapidly, repair proteins will redistribute to the damaged region. Boal et al. used atomic force microscopy to establish that redistribution did take place in complexes of the BER enzyme EndoIII with DNA duplexes containing a single mismatch. As predicted, cooperation was observed between different BER enzymes, the bacterial EndoIII and MutY. These enzymes have human homologs linked to cancer predisposition, although the medical implications of the conservation of these iron-sulfur clusters remain unclear. Proc. Natl. Acad. Sci. U.S.A. 106 , 15237 (2009). [1]: pending:yes