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Updated: Oct 13, 2025

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

Suresh S Pujari1, Natalia Tretyakova1

  • 1Department of Medicinal Chemistry and Masonic Cancer Center, University of Minnesota, Minneapolis, MN, United States.

Methods in Enzymology
|November 15, 2021
PubMed

Insights

DNA-peptide cross-links (DpCs) and DNA-protein cross-links (DPCs) are DNA damage. DPCs are degraded to DpCs, which are bypassed by DNA polymerases, but efficiency varies with peptide characteristics.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • DNA-peptide (DpCs) and DNA-protein cross-links (DPCs) are DNA lesions that impede vital cellular processes.
  • Large DPCs pose significant challenges to cell survival by blocking DNA replication, transcription, and repair.

Purpose of the Study:

  • To explore synthetic methods for generating DpCs and DPCs.
  • To investigate the impact of DpCs and DPCs on DNA polymerase activity and fidelity.

Main Methods:

  • Synthetic generation of DpCs and DPCs using reductive amination and oxime ligation.
  • Biochemical assays to assess DNA polymerase bypass efficiency and fidelity.

Main Results:

  • DpCs are formed from DPCs via proteolytic degradation.
  • Translesion synthesis (TLS) DNA polymerases can bypass DpCs.
  • Bypass efficiency and accuracy are influenced by peptide size, sequence, and position within DpCs.

Conclusions:

  • DpCs and DPCs are significant DNA lesions requiring cellular repair mechanisms.
  • Understanding DpC and DPC formation and processing is crucial for comprehending DNA damage response pathways.
  • TLS polymerases play a key role in navigating DpC lesions, with lesion characteristics dictating bypass outcomes.
Keywords:
BioconjugationDNA polymeraseDNA-protein cross linksHistoneOxime ligationPolymerase bypassReductive aminationSortase mediated ligation

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