Abstract:
:The DNA repair enzyme human uracil DNA glycosylase (UNG) scans short stretches of genomic DNA and captures rare uracil bases as they transiently emerge from the DNA duplex via spontaneous base pair breathing motions. The process of DNA scanning requires that the enzyme transiently loosen its grip on DNA to allow stochastic movement along the DNA contour, while engaging extrahelical bases requires motions on a more rapid timescale. Here, we use NMR dynamic measurements to show that free UNG has no intrinsic dynamic properties in the millisecond to microsecond and subnanosecond time regimes, and that the act of binding to nontarget DNA reshapes the dynamic landscape to allow productive millisecond motions for scanning and damage recognition. These results suggest that DNA structure and the spontaneous dynamics of base pairs may drive the evolution of a protein sequence that is tuned to respond to this dynamic regime.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Friedman JI,Majumdar A,Stivers JTdoi
10.1093/nar/gkp161subject
Has Abstractpub_date
2009-06-01 00:00:00pages
3493-500issue
11eissn
0305-1048issn
1362-4962pii
gkp161journal_volume
37pub_type
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