Environmental and Molecular Mutagenesis (EMM) Editor's Choice - October 2011
The Editor's Choice for October is "XRCC1 Coordinates Disparate Responses and Multiprotein Repair Complexes Depending on the Nature and Context of the DNA Damage" by Audun Hanssen-Bauer, Karin Solvang-Garten, Ottar Sundheim, Javier Pena-Diaz, Sonja Andersen, Geir Slupphaug, Hans E. Krokan, David M. Wilson, Mansour Akbari, and Marit Otterlei.
Audun Hanssen-Bauer and colleagues explored the function of the XRCC1 scaffold protein in the repair of base lesions and single-strand breaks. They expressed fluorescently-tagged XRCC1 and fractionated nuclear extracts. They identified different sized protein complexes that included the XRCC1 protein. Additional proteins present in one or more of those complexes included Lig III, POLδ, PNK, POLβ, PCNA and UNG2. Next, using different types of “damaged” substrates and inhibitors, Hanssen-Bauer and colleagues obtained evidence that complexes containing XRCC1 are capable of both short patch and long patch base excision repair. The repair proficiencies possessed by the different XRCC1-containing complexes were characterized. Audun Hanssen-Bauer and colleagues used time-lapse photography and localized micro-irradiation to visualize the recruitment of repair complex proteins to foci where DNA damage was undergoing repair, and to show that the type of foci generated varied with the dose of micro-irradiation. With this new and detailed mechanistic information, Hanssen-Bauer and colleagues developed a model describing three modes of base excision. According to their model, three distinct complexes may form through recruitment of different base excision repair proteins onto an XRCC1 core complex, depending on the nature of the damage. Thus, the elegant biochemical and microscopy-based experiments by Hanssen-Bauer et al. extend current understanding regarding the molecular complexity involved in the repair of base lesions and single-strand breaks in DNA. Environ. Mol. Mutagen. 52:623-635 (2011) Published 2011 Wiley-Liss, Inc.