The p-benzoquinone DNA adducts derived from benzene are highly mutagenic

Zhongwen Xie, Yangbin Zhang, Anton B. Guliaev, Huiyun Shen, Bo Hang, B. Singer, Zhigang Wang

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Benzene is a human leukemia carcinogen, resulting from its cellular metabolism. A major benzene metabolite is p-benzoquinone (pBQ), which can damage DNA by forming the exocyclic base adducts pBQ-dC, pBQ-dA, and pBQ-dG in vitro. To gain insights into the role of pBQ in benzene genotoxicity, we examined in vitro translesion synthesis and in vivo mutagenesis of these pBQ adducts. Purified REV1 and Polκ were essentially incapable of translesion synthesis in response to the pBQ adducts. Opposite pBQ-dA and pBQ-dC, purified human Polι was capable of error-prone nucleotide insertion, but was unable to perform extension synthesis. Error-prone translesion synthesis was observed with Polη. However, DNA synthesis largely stopped opposite the lesion. Consistent with in vitro results, replication of site-specifically damaged plasmids was strongly inhibited by pBQ adducts in yeast cells, which depended on both Polζ and Polη. In wild-type cells, the majority of translesion products were deletions at the site of damage, accounting for 91%, 90%, and 76% for pBQ-dA, pBQ-dG, and pBQ-dC, respectively. These results show that the pBQ-dC, pBQ-dA, and pBQ-dG adducts are strong blocking lesions, and are highly mutagenic by predominantly inducing deletion mutations. These results are consistent with the lesion structures predicted by molecular dynamics simulation. Our results led to the following model. Translesion synthesis normally occurs by directly copying the lesion site through base insertion and extension synthesis. When the lesion becomes incompatible in accommodating a base opposite the lesion in DNA, translesion synthesis occurs by a less efficient lesion loop-out mechanism, resulting in avoiding copying the damaged base and leading to deletion.

Original languageEnglish
Pages (from-to)1399-1409
Number of pages11
JournalDNA Repair
Issue number12
StatePublished - Dec 8 2005

Bibliographical note

Funding Information:
This work was supported by NIH grants CA92528 (to Z. W.), CA47723 (to B. S.), and CA72079 (to B. H.).


  • Benzene
  • DNA adducts
  • Lesion bypass
  • Mutagenesis
  • Polymerase ζ
  • Translesion synthesis
  • Y family DNA polymerase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'The p-benzoquinone DNA adducts derived from benzene are highly mutagenic'. Together they form a unique fingerprint.

Cite this