Participation of TDP1 in the repair of formaldehyde-induced DNA-protein crosslinks in chicken DT40 cells

Toshiaki Nakano, Mahmoud I. Shoulkamy, Masataka Tsuda, Hiroyuki Sasanuma, Kouji Hirota, Minoru Takata, Shin Ichiro Masunaga, Shunichi Takeda, Hiroshi Ide, Tadayoshi Bessho, Keizo Tano

Research output: Contribution to journalArticle

Abstract

Proteins are covalently trapped on DNA to form DNA-protein cross-links (DPCs) when cells are exposed to DNA-damaging agents. Aldehyde compounds produce common types of DPCs that contain proteins in an undisrupted DNA strand. Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs topoisomerase 1 (TOPO1) that is trapped at the 3’-end of DNA. In the present study, we examined the contribution of TDP1 to the repair of formaldehyde-induced DPCs using a reverse genetic strategy with chicken DT40 cells. The results obtained showed that cells deficient in TDP1 were sensitive to formaldehyde. The removal of formaldehyde-induced DPCs was slower in tdp1-deficient cells than in wild type cells. We also found that formaldehyde did not produce trapped TOPO1, indicating that trapped TOPO1 was not a primary cytotoxic DNA lesion that was generated by formaldehyde and repaired by TDP1. The formaldehyde treatment resulted in the accumulation of chromosomal breakages that were more prominent in tdp1-deficient cells than in wild type cells. Therefore, TDP1 plays a critical role in the repair of formaldehyde-induced DPCs that are distinct from trapped TOPO1.

Original languageEnglish (US)
Article numbere0234859
JournalPloS one
Volume15
Issue number6 June
DOIs
StatePublished - Jun 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Nakano, T., Shoulkamy, M. I., Tsuda, M., Sasanuma, H., Hirota, K., Takata, M., Masunaga, S. I., Takeda, S., Ide, H., Bessho, T., & Tano, K. (2020). Participation of TDP1 in the repair of formaldehyde-induced DNA-protein crosslinks in chicken DT40 cells. PloS one, 15(6 June), [e0234859]. https://doi.org/10.1371/journal.pone.0234859