Cell Growth & Differentiation, Vol 5, Issue 5 485-494, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Down-regulation of genes encoding DNA replication proteins during cell cycle exit

AL Moore and TS Wang
Department of Pathology, Stanford University School of Medicine, California 94305.

We have studied the expression of genes encoding DNA replication proteins during different cell growth events. Gene expression of human DNA polymerase alpha-DNA primase, a principal chromosomal replication enzyme complex, is up-regulated during the entrance of a cell from quiescence into the mitotic cell cycle. In contrast, expression of these genes is greatly reduced in fibroblasts rendered temporarily quiescent by contact inhibition or serum starvation. In actively cycling cells, DNA polymerase alpha-DNA primase genes are expressed at all stages of the cell cycle. To investigate how their gene expression is regulated in cells permanently exiting the cell cycle during terminal differentiation, we used a novel method to obtain a pure population of such cells. In this report, we describe the down-regulation of gene expression of DNA polymerase alpha during both HL-60 (human myeloid) and MEL (mouse erythroleukemia) cell differentiation. Gene expression of the two subunits of DNA primase, p49 and p58, is also down-regulated at the mRNA level in differentiated MEL cells. In differentiated HL-60 cells, the decline of DNA polymerase alpha gene expression occurs at both the transcript and protein levels. Down-regulation of DNA polymerase alpha at the steady state transcript level is caused, at least in part, by a decreased rate of transcription initiation without transcription elongation block.

This article has been cited by other articles:

				W.-M. Chien, J. N. Parker, D.-C. Schmidt-Grimminger, T. R. Broker, and L. T. Chow Casein Kinase II Phosphorylation of the Human Papillomavirus-18 E7 Protein Is Critical for Promoting S-Phase Entry Cell Growth Differ., August 1, 2000; 11(8): 425 - 435. [Abstract] [Full Text]

				Y. Jian, B. A. Van Tine, W.-M. Chien, G. M. Shaw, T. R. Broker, and L. T. Chow Concordant Induction of Cyclin E and p21cip1 in Differentiated Keratinocytes by the Human Papillomavirus E7 Protein Inhibits Cellular and Viral DNA Synthesis Cell Growth Differ., February 1, 1999; 10(2): 101 - 111. [Abstract] [Full Text]

				J. A. Pitcher, R. A. Hall, Y. Daaka, J. Zhang, S. S. G. Ferguson, S. Hester, S. Miller, M. G. Caron, R. J. Lefkowitz, and L. S. Barak The G Protein-coupled Receptor Kinase 2 Is a Microtubule-associated Protein Kinase That Phosphorylates Tubulin J. Biol. Chem., May 15, 1998; 273(20): 12316 - 12324. [Abstract] [Full Text] [PDF]

				B. Li and M. Y. W. Lee Transcriptional Regulation of the Human DNA Polymerase delta Catalytic Subunit Gene POLD1 by p53 Tumor Suppressor and Sp1 J. Biol. Chem., August 3, 2001; 276(32): 29729 - 29739. [Abstract] [Full Text] [PDF]