HaiYan Jianga,e, Robert J. Hickeya-e, h, Pamela E. Bechtelf, Philip
W. Willsa, e, SuHua Hana,e, Timothy D. Toma-g, YueTong Weia,e, and Linda
H. Malkasa-e,+, (a) Department of Pharmacology and Experimental Therapeutics
(b) Program in Molecular and Cellular Biology (c) Program in Oncology
(d) Program in Toxicology (e) University of Maryland School of Medicine
(f) University of Maryland School of Pharmacy (g) Department of Anesthesiology
(h) Marlene and Stewart Greenebaum Cancer Center, 685 W. Baltimore St.,
Baltimore, MD 21201.
+ Author to whom correspondence should be addressed.
The process of DNA replication is an important regulatory point for modulating cell proliferation. The elucidation of the role played by the human DNA replication apparatus, and its components, in this regulatory process is anticipated to further our understanding of both normal and cancer cell proliferation. The concept that many enzymes and factors involved in the replication of mammalian DNA function together as an organized multiprotein complex has been supported by increasing evidence [reviewed in reference 1]. We have previously reported that a highly purified multiprotein form of DNA polymerase can be isolated from a variety of mammalian cell types and tissues.26 We have shown that this multiprotein form of DNA polymerase, designated the DNA synthesome, is fully competent to support origin DNA sequence specific large T-antigen-dependent papovavirus DNA replication in vitro.26 The DNA synthesome was purified from cells using a series of steps which included centrifugati