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Regulation of cyclin G1 during murine hepatic regeneration following dipin‐induced DNA damage
Author(s) -
Jensen Michael Rugaard,
Factor Valentina M.,
Thorgeirsson Snorri S.
Publication year - 1998
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510280235
Subject(s) - cyclin a , cell cycle , cyclin b , cyclin b1 , microbiology and biotechnology , cyclin e , biology , g2 m dna damage checkpoint , cell cycle checkpoint , cyclin a2 , cyclin , cyclin d , mitosis , cyclin d1 , cell growth , dna damage , dna synthesis , cancer research , cyclin dependent kinase 1 , cell , biochemistry , dna
Cyclin G1 has been linked to both positive and negative growth regulation. The expression of cyclin G1 is induced by transforming growth factor β 1 and p53, as well as by multiple mitogenic stimuli in mammalian cells in culture. However, the physiological role of cyclin G1 remains unclear. To examine the cell‐cycle regulation of cyclin G1 in vivo , two models of coordinated cell proliferation induced by partial hepatectomy (PH) in the presence or absence of DNA damage were used. To introduce DNA damage, mice were treated with the alkylating drug, 1,4‐bis[ N , N ′‐di(ethylene)‐phosphamide]piperazine (Dipin) 2 hours before PH. Cell‐cycle progression was monitored by 5‐bromo‐2‐deoxyuridine (BrdU) incorporation into the DNA, the frequency of mitoses, the expression of cell‐cycle control genes, and by flow cytometry. Dipin treatment resulted in cell‐cycle arrest at the G2/M boundary without affecting G0/G1 and G1/S transitions. While the hepatocytes progressively entered G2 phase arrest, the cyclin G1 mRNA and protein levels increased more than five‐ and eightfold, respectively. Cyclin G1 had a nuclear localization in all interphase cells with clear absence from nucleoli. In contrast, during mitosis, cyclin G1 was undetectable by immunohistochemistry. Taken together, our data provide evidence for a putative role of cyclin G1 in G2/M checkpoint control.