Synthesis and polymerase bypass studies of DNA-peptide and DNA-protein conjugates

Suresh S. Pujari, Natalia Tretyakova

Research output: Chapter in Book/Report/Conference proceedingChapter


DNA-peptide (DpCs) and DNA-protein cross-links (DPCs) are DNA lesions formed when polypeptides and nuclear proteins become covalently trapped on DNA strands. DNA-protein cross-links are of enormous size and hence pose challenges to cell survival by blocking DNA replication, transcription, and repair. However, DPCs can undergo proteolytic degradation via various pathways to give shorter polypeptide chains (DpCs). The resulting DpC lesions are efficiently bypassed by translesion synthesis (TLS) DNA polymerases like κ, η, δ, etc., although polymerase bypass efficiency as well as correct base insertion depends heavily on size, sequence context, and position of peptides in DpCs. This chapter explores various synthetic methods to generate these lesions including detailed experimental procedures for the construction of DpCs and DPCs via reductive amination and oxime ligation. Further we describe biochemical experiments to investigate the effects of these lesions on DNA polymerase activity and fidelity.

Original languageEnglish (US)
Title of host publicationThe DNA Replication-Repair Interface
EditorsBrandt F. Eichman
PublisherAcademic Press Inc.
Number of pages43
ISBN (Print)9780323907330
StatePublished - Jan 2021

Publication series

NameMethods in enzymology
PublisherAcademic Press Inc.
ISSN (Print)0076-6879

Bibliographical note

Funding Information:
We would like to thank Robert Carlson (University of Minnesota Cancer Center) for his help preparing the figures and acquiring the reprint permissions. This work is supported by an R01 grant from the NEIHS (ES-023350).

Publisher Copyright:
© 2021 Elsevier Inc.


  • Bioconjugation
  • DNA polymerase
  • DNA-protein cross links
  • Histone
  • Oxime ligation
  • Polymerase bypass
  • Reductive amination
  • Sortase mediated ligation

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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