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Reoxygenation following hypoxia activates DNA‐damage checkpoint signaling pathways that suppress cell‐cycle progression in cultured human lymphocytes
Author(s) -
Kim Byeong-Mo,
Choi Jun Yeol,
Kim Yang-Jee,
Woo Hae-Dong,
Chung Hai Won
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.05.053
Subject(s) - g2 m dna damage checkpoint , cell cycle checkpoint , dna damage , chek1 , cell cycle , cyclin dependent kinase 1 , microbiology and biotechnology , phosphorylation , checkpoint kinase 2 , biology , cytokinesis , dna repair , signal transduction , apoptosis , cancer research , cell division , cell , dna , biochemistry
Cellular responses to DNA damage after hypoxia and reoxygenation (H/R) were examined in human lymphocytes. Cultured lymphocytes exposed to H/R showed a lower cytokinesis block proliferation index and a higher frequency of micronuclei in comparison to control cells. Western blots showed that H/R exposure induced p53 expression; however, p21 and Bax expression did not increase, indicating that H/R did not affect p53 transactivational activity. Phosphorylation of p53 (Ser15), Chk1 (Ser345), and Chk2 (Thr68) was also observed, suggesting that H/R activates p53 through checkpoint signals. In addition, H/R exposure caused the phosphorylation and negative regulation of Cdc2 and Cdc25C, proteins that are involved in cell‐cycle arrest at the G2/M checkpoint. The S‐phase checkpoint, regulated by the ATM‐p95/NBS1–SMC1 pathway, was also triggered in H/R‐exposed lymphocytes. These results demonstrate that H/R exposure triggers checkpoint signaling and induces cell‐cycle arrest in cultured human lymphocytes.