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E2F1 enhances 8-Chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells

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Abstract

The E2F1 transcription factor is a well known regulator of cell proliferation and apoptosis, but its role in response to DNA damage is less clear. 8-Chloro-adenosine (8-Cl-Ado), a nucleoside analog, can inhibit proliferation in a variety of human tumor cells. However, it is still elusive how the agent acts on tumors. Here we show that A549 and H1299 cells formed DNA double-strand breaks after 8-Cl-Ado exposure, accompanied by E2F1 upregulation at protein level. Overexpressed wild-type (E2F1-wt) colocalized with double-strand break marker γ-H2AX and promoted G2/M arrest in 8-Cl-Ado-exposed A549 and H1299, while expressed S31A mutant of E2F1 (E2F1-mu) significantly reduced ability to accumulate at sites of DNA damage and G2/M arrest, suggesting that E2F1 is required for activating G2/M checkpoint pathway upon DNA damage. Transfection of either E2F1-wt or E2F1-mu plasmid promoted apoptosis in 8-Cl-Ado-exposed cells, indicating that 8-Cl-Ado may induce apoptosis in E2F1-dependent and E2F1-independent ways. These findings demonstrate that E2F1 plays a crucial role in 8-Cl-Ado-induced G2/M arrest but is dispensable for 8-Cl-Ado-induced apoptosis. These data also suggest that the mechanism of 8-Cl-Ado action is complicated.

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Abbreviations

ATM:

ataxia telangiectasia mutated

ATR:

ATM and Rad3-related kinase

BRCA1:

breast cancer type 1 susceptibility protein

CHK2:

checkpoint kinase 2

8-Cl-Ado:

8-chloro-adenosine

8-Cl-cAMP:

8-chloro-cAMP

DSB:

double-strand break

NER:

nucleotide excision repair

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Xue Yuan Road 38, Beijing, 100191, PR China

    Hong-Ying Duan, Ji-Xiang Cao, Jun-Juan Qi, Guo-Sheng Wu, Shu-Yan Li, Guo-Shun An, Hong-Ti Jia & Ju-Hua Ni

  2. Department of Biochemistry, Hainan Medical College, Haikou, 571101, PR China

    Hong-Ying Duan & Wang-Wei Cai

  3. Department of Biochemistry and Molecular Biology, Capital University of Medical Sciences, You An Men Xitoutiao 8, Beijing, 100054, PR China

    Hong-Ti Jia

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  1. Hong-Ying Duan
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Correspondence to Ju-Hua Ni.

Additional information

Published in Russian in Biokhimiya, 2012, Vol. 77, No. 3, pp. 330–341.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM11-224, January 22, 2012.

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Duan, HY., Cao, JX., Qi, JJ. et al. E2F1 enhances 8-Chloro-adenosine-induced G2/M arrest and apoptosis in A549 and H1299 lung cancer cells. Biochemistry Moscow 77, 261–269 (2012). https://doi.org/10.1134/S0006297912030042

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  • DOI: https://doi.org/10.1134/S0006297912030042

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