Structure of a trapped endonuclease III-DNA covalent intermediate

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Single-Molecule Dwell-Time Analysis of Restriction Endonuclease-Mediated DNA Cleavage
09:53

Single-Molecule Dwell-Time Analysis of Restriction Endonuclease-Mediated DNA Cleavage

Published on: February 7, 2021

J Christopher Fromme1, Gregory L Verdine

  • 1Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.

The EMBO Journal
|July 4, 2003
PubMed

Insights

Endonuclease III (EndoIII) repairs oxidative DNA damage by removing damaged bases. Its crystal structure reveals how it recognizes diverse DNA lesions, offering insights into cancer-related mutations in similar repair proteins.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Cells possess DNA repair proteins to counteract oxidative DNA damage.
  • The base-excision repair (BER) pathway is crucial for mitigating toxicity from oxidized nucleobase lesions.
  • Endonuclease III (EndoIII) is a DNA glycosylase that repairs oxidized pyrimidine lesions in DNA.

Purpose of the Study:

  • To elucidate the mechanism of DNA repair by Endonuclease III.
  • To understand how EndoIII recognizes and repairs various oxidatively damaged DNA bases.
  • To investigate potential links between EndoIII function and cancer-associated mutations.

Main Methods:

  • Determined the crystal structure of a trapped intermediate of Endonuclease III bound to DNA.
  • Utilized structural analysis to infer the DNA recognition and repair process.

Main Results:

  • Captured a crystal structure of Endonuclease III (EndoIII) during DNA repair.
  • The structure provides mechanistic insights into EndoIII's recognition of diverse oxidatively damaged DNA bases.
  • The findings suggest a reason for mutations in the related human DNA repair protein MYH found in cancers.

Conclusions:

  • The crystal structure of the EndoIII-DNA complex illuminates the repair mechanism for oxidative DNA damage.
  • Understanding EndoIII's function is vital for comprehending DNA repair pathways and their implications in human diseases like cancer.

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