5-Formylcytosine Yields DNA-Protein Cross-Links in Nucleosome Core Particles

J Am Chem Soc. 2017 Aug 9;139(31):10617-10620. doi: 10.1021/jacs.7b05495. Epub 2017 Jul 25.

Abstract

In situ generation of 5-formylcytosine (5fC) in nucleosome core particles (NCPs) reveals that 5fC leads to essential DNA-protein cross-links (DPCs). Mechanistic studies using chemical models and mutated histones demonstrate that DPCs form reversibly between the formyl function of 5fC and primary amines on histones. These results suggest that DPC formation from 5fC in chromatin occurs in addition to its role in DNA demethylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • DNA / chemistry
  • DNA / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Kinetics
  • Models, Biological
  • Molecular Structure
  • Nucleosomes / chemistry*
  • Proteins / chemistry
  • Proteins / metabolism*
  • Schiff Bases / chemistry

Substances

  • 5-formylcytosine
  • Nucleosomes
  • Proteins
  • Schiff Bases
  • Cytosine
  • DNA