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.


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: Translesion synthesis of 6-nitrochrysene-derived 2'-deoxyadenosine adduct in human cells.

Authors: Powell, Brent V; Bacurio, Jan Henric T; Basu, Ashis K

Published In DNA Repair (Amst), (2020 11)

Abstract: 6-Nitrochrysene (6-NC) is a potent mutagen in bacteria and carcinogenic in animals. It is the most potent carcinogen ever tested in newborn mouse assay. DNA lesions resulting from 6-NC modification are likely to induce mutations if they are not removed by cellular defense pathways prior to DNA replication. Earlier studies showed that 6-NC-derived C8-2'-deoxyadenosine adduct, N-(dA-8-yl)-6-AC, is very slowly repaired in human cells. In this study, we have investigated replication of N-(dA-8-yl)-6-AC in human embryonic kidney (HEK 293T) cells and the roles of translesion synthesis (TLS) DNA polymerases in bypassing it. Replication of a plasmid containing a single site-specific N-(dA-8-yl)-6-AC adduct in HEK 293 T cells showed that human DNA polymerase (hPol) η and hPol κ played important roles in bypassing the adduct, since TLS efficiency was reduced to 26 % in the absence of these two polymerases compared to 83 % in polymerase-competent HEK 293T cells. The progeny from HEK 293T cells provided 12.7 % mutants predominantly containing A→T transversions. Mutation frequency (MF) was increased to 17.8 % in hPol η-deficient cells, whereas it was decreased to 3.3 % and 3.9 % when the adduct containing plasmid was replicated in hPol κ- and hPol ζ-deficient cells, respectively. The greatest reduction in MF by more than 90 % (to MF 1.2 %) was observed in hPol ζ-knockout cells in which hPol κ was knocked down. Taken together, these results suggest that hPol κ and hPol ζ are involved in the error-prone TLS of N-(dA-8-yl)-6-AC, while hPol η performs error-free bypass.

PubMed ID: 32721818 Exiting the NIEHS site

MeSH Terms: Chrysenes/chemistry*; DNA Adducts/chemistry; DNA Adducts/metabolism*; DNA Repair*; DNA Replication; DNA-Binding Proteins/metabolism*; DNA-Directed DNA Polymerase/metabolism*; Deoxyadenosines/chemistry*; HEK293 Cells; Humans

to Top