Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Site-Specific 5-Formyl Cytosine Mediated DNA-Histone Cross-Links: Synthesis and Polymerase Bypass by Human DNA Polymerase η.

Authors: Pujari, Suresh S; Wu, Mingxuan; Thomforde, Jenna; Wang, Zhipeng A; Chao, Christopher; Olson, Noelle M; Erber, Luke; Pomerantz, William C K; Cole, Philip; Tretyakova, Natalia Y

Published In Angew Chem Int Ed Engl, (2021 12 13)

Abstract: DNA-protein cross-links (DPCs) between DNA epigenetic mark 5-formylC and lysine residues of histone proteins spontaneously form in human cells. Such conjugates are likely to influence chromatin structure and mediate DNA replication, transcription, and repair, but are challenging to study due to their reversible nature. Here we report the construction of site specific, hydrolytically stable DPCs between 5fdC in DNA and K4 of histone H3 and an investigation of their effects on DNA replication. Our approach employs oxime ligation, allowing for site-specific conjugation of histones to DNA under physiological conditions. Primer extension experiments revealed that histone H3-DNA crosslinks blocked DNA synthesis by hPol η polymerase, but were bypassed following proteolytic processing.

PubMed ID: 34634172 Exiting the NIEHS site

MeSH Terms: Cytosine/chemistry; Cytosine/metabolism*; DNA-Directed DNA Polymerase/metabolism*; DNA/chemistry; DNA/metabolism*; Histones/chemistry; Histones/metabolism*; Humans; Molecular Structure

Back
to Top