Strandwise translocation of a DNA glycosylase on undamaged DNA

Journal Article · Mon May 14 04:00:00 EDT 2012 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.1111237108· OSTI ID:1034214

Qi, Yan; Nam, Kwangho; Spong, Marie C; Banerjee, Anirban; Sung, Rou-Jia; Zhang, Michael; Karplus, Martin; Verdine, Gregory L ^[1]

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1. Harvard

Base excision repair of genotoxic nucleobase lesions in the genome is critically dependent upon the ability of DNA glycosylases to locate rare sites of damage embedded in a vast excess of undamaged DNA, using only thermal energy to fuel the search process. Considerable interest surrounds the question of how DNA glycosylases translocate efficiently along DNA while maintaining their vigilance for target damaged sites. Here, we report the observation of strandwise translocation of 8-oxoguanine DNA glycosylase, MutM, along undamaged DNA. In these complexes, the protein is observed to translocate by one nucleotide on one strand while remaining untranslocated on the complementary strand. We further report that alterations of single base-pairs or a single amino acid substitution (R112A) can induce strandwise translocation. Molecular dynamics simulations confirm that MutM can translocate along DNA in a strandwise fashion. These observations reveal a previously unobserved mode of movement for a DNA-binding protein along the surface of DNA.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: NSFOTHERNIHHHMI
• OSTI ID: 1034214
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (4) ; 01, 2012 Vol. 109; ISSN 1091-6490
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
AMINO ACIDS
CROSS-LINKING
DISULFIDES
DNA
EXCISION REPAIR
NUCLEOTIDES
PROTEINS
TARGETS
TRANSLOCATION