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Title: Structure of a DNA Glycosylase Searching for Lesions

Journal Article · · Science

DNA glycosylases must interrogate millions of base pairs of undamaged DNA in order to locate and then excise one damaged nucleobase. The nature of this search process remains poorly understood. Here we report the use of disulfide cross-linking (DXL) technology to obtain structures of a bacterial DNA glycosylase, MutM, interrogating undamaged DNA. These structures, solved to 2.0 angstrom resolution, reveal the nature of the search process: The protein inserts a probe residue into the helical stack and severely buckles the target base pair, which remains intrahelical. MutM therefore actively interrogates the intact DNA helix while searching for damage.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
Sponsoring Organization:
Doe - Office Of Science
DOE Contract Number:
DE-AC02-98CH10886
OSTI ID:
914262
Report Number(s):
BNL-78830-2007-JA; SCEHDK; TRN: US200809%%123
Journal Information:
Science, Vol. 311; ISSN 0193-4511
Country of Publication:
United States
Language:
English