Nontarget DNA binding shapes the dynamic landscape for enzymatic recognition of DNA damage.

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 Res

journal_title

Nucleic acids research

authors

Friedman JI,Majumdar A,Stivers JT

doi

10.1093/nar/gkp161

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

3493-500

issue

11

eissn

0305-1048

issn

1362-4962

pii

gkp161

journal_volume

37

pub_type

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