title: Sculpting of DNA at abasic sites by DNA glycosylase homolog mag2.
abstract: Modifications and loss of bases are frequent types of DNA lesions, often handled by the base excision repair (BER) pathway. BER is initiated by DNA glycosylases, generating abasic (AP) sites that are subsequently cleaved by AP endonucleases, which further pass on nicked DNA to downstream DNA polymerases and ligases. The coordinated handover of cytotoxic intermediates between different BER enzymes is most likely facilitated by the DNA conformation. Here, we present the atomic structure of Schizosaccharomyces pombe Mag2 in complex with DNA to reveal an unexpected structural basis for nonenzymatic AP site recognition with an unflipped AP site. Two surface-exposed loops intercalate and widen the DNA minor groove to generate a DNA conformation previously only found in the mismatch repair MutS-DNA complex. Consequently, the molecular role of Mag2 appears to be AP site recognition and protection, while possibly facilitating damage signaling by structurally sculpting the DNA substrate.
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Dalhus
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway.
authors.forename: Line
authors.initials: L
authors.lastname: Nilsen
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Korvald
authors.affiliation: Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Joy
authors.initials: J
authors.lastname: Huffman
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway.
authors.forename: Rune Johansen
authors.initials: RJ
authors.lastname: Forstrøm
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic and Foundation, Rochester, MN 55905, USA; Department of Genome Dynamics, Lawrence Berkeley National Laboratory, One Cyclotron Road, Mailstop: 83R0101, Berkeley, CA 94720, USA.
authors.forename: Cynthia T
authors.initials: CT
authors.lastname: McMurray
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway. Electronic address: ingrun.alseth@rr-research.no.
authors.forename: Ingrun
authors.initials: I
authors.lastname: Alseth
authors.affiliation: Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Bioenergy/GTL and Structural Biology, Lawrence Berkeley National Laboratory, One Cyclotron Road, Mailstop: 83R0101, Berkeley, CA 94720, USA. Electronic address: jat@scripps.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Tainer
authors.affiliation: Department of Microbiology, Centre of Molecular Biology and Neuroscience, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, PO Box 4950, Nydalen, N-0424, Oslo, Norway; Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: magnar.bjoras@rr-research.no.
authors.forename: Magnar
authors.initials: M
authors.lastname: Bjørås
mesh_terms: D000595:Amino Acid Sequence; D001080:Apurinic Acid / Q000737:chemistry*; D020029:Base Pairing; D001665:Binding Sites; D018360:Crystallography, X-Ray; D045647:DNA Glycosylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004271:DNA, Fungal / Q000737:chemistry; D004843:Epistasis, Genetic; D055786:Gene Knockout Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012568:Schizosaccharomyces / Q000201:enzymology* / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D004271:DNA, Fungal; D029702:Schizosaccharomyces pombe Proteins; D001080:Apurinic Acid; D045647:DNA Glycosylases; C581961:Mag2 protein, S pombe; D051719:MutS DNA Mismatch-Binding Protein