TY - JOUR
T1 - Participation of TDP1 in the repair of formaldehyde-induced DNA-protein crosslinks in chicken DT40 cells
AU - Nakano, Toshiaki
AU - Shoulkamy, Mahmoud I.
AU - Tsuda, Masataka
AU - Sasanuma, Hiroyuki
AU - Hirota, Kouji
AU - Takata, Minoru
AU - Masunaga, Shin Ichiro
AU - Takeda, Shunichi
AU - Ide, Hiroshi
AU - Bessho, Tadayoshi
AU - Tano, Keizo
N1 - Funding Information:
This work was directly supported by JSPS KAKENHI grant numbers 18K11640 to KT, 19K22561 and 16H06306 to ST, and 18H04900 and 19H04267 to HS. This work was supported by JSPS Core-to-Core Program, Advanced Research Networks to ST. We are grateful to Haruna Fujiike for her technical assistance and to Dr. Takahito Moriwaki for the statistical analysis. We thank Noriko Tano for her secretarial assistance.
Publisher Copyright:
© 2020 Nakano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0234859
DO - 10.1371/journal.pone.0234859
M3 - Article
C2 - 32589683
AN - SCOPUS:85087320141
SN - 1932-6203
VL - 15
JO - PloS one
JF - PloS one
IS - 6 June
M1 - e0234859
ER -