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Replitase: Complete machinery for DNA synthesis
Author(s) -
Murthy Shalini,
Reddy G. PremVeer
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20842
Subject(s) - dna replication , biology , eukaryotic dna replication , origin recognition complex , licensing factor , control of chromosome duplication , dna synthesis , s phase , dna , replication factor c , microbiology and biotechnology , pre replication complex , cell cycle , genetics , cell
Replication of nuclear DNA in eukaryotes presents a tremendous challenge, not only due to the size and complexity of the genome, but also because of the time constraint imposed by a limited duration of S phase during which the entire genome has to be duplicated accurately and only once per cell division cycle. A challenge of this magnitude can only be met by the close coupling of DNA precursor synthesis to replication. Prokaryotic systems provide evidence for multienzyme and multiprotein complexes involved in DNA precursor synthesis and DNA replication. In addition, fractionation of nuclear proteins from proliferating mammalian cells shows co‐sedimentation of enzymes involved in DNA replication with those required for synthesis of deoxynucleoside triphosphates (dNTPs). Such complexes can be isolated only from cells that are in S phase, but not from cells in G 0 /G 1 phases of cell cycle. The kinetics of deoxynucleotide metabolism supporting DNA replication in intact and permeabilized cells reveals close coupling and allosteric interaction between the enzymes of dNTP synthesis and DNA replication. These interactions contribute to channeling and compartmentation of deoxynucleotides in the microvicinity of DNA replication. A multienzyme and multiprotein megacomplex with these unique properties is called “replitase.” In this article, we summarize some of the relevant evidence to date that supports the concept of replitase in mammalian cells, which originated from the observations in Dr. Pardee's laboratory. In addition, we show that androgen receptor (AR), which plays a critical role in proliferation and viability of prostate cancer cells, is associated with replitase, and that identification of constituents of replitase in androgen‐dependent versus androgen‐independent prostate cancer cells may provide insights into androgen‐regulated events that control proliferation of prostate cancer cells and potentially offer an effective strategy for the treatment of prostate cancer. J. Cell. Physiol. 209: 711–717, 2006. © 2006 Wiley‐Liss, Inc.