|
|
|
|
Vol. 13, Issue 2, 607-620, February 2002
Department of Genetics, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104
Duplication of the eukaryotic genome initiates from multiple
origins of DNA replication whose activity is coordinated with the cell
cycle. We have been studying the origins of DNA replication that
control amplification of eggshell (chorion) genes during Drosophila oogenesis. Mutation of genes required for
amplification results in a thin eggshell phenotype, allowing a genetic
dissection of origin regulation. Herein, we show that one mutation
corresponds to a subunit of the minichromosome maintenance (MCM)
complex of proteins, MCM6. The binding of the MCM complex to origins in
G1 as part of a prereplicative complex is critical for the cell
cycle regulation of origin licensing. We find that MCM6 associates with other MCM subunits during amplification. These results suggest that
chorion origins are bound by an amplification complex that contains MCM
proteins and therefore resembles the prereplicative complex. Lethal
alleles of MCM6 reveal it is essential for mitotic cycles and
endocycles, and suggest that its function is mediated by ATP. We
discuss the implications of these findings for the role of MCMs in the
coordination of DNA replication during the cell cycle.
Corresponding author. E-mail address:
Calvi{at}mail.med.upenn.edu.
This article has been cited by other articles:
![]() |
G. Mlechkovich and N. Frenkel Human Herpesvirus 6A (HHV-6A) and HHV-6B Alter E2F1/Rb Pathways and E2F1 Localization and Cause Cell Cycle Arrest in Infected T Cells J. Virol., December 15, 2007; 81(24): 13499 - 13508. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. R. Calvi, B. A. Byrnes, and A. J. Kolpakas Conservation of Epigenetic Regulation, ORC Binding and Developmental Timing of DNA Replication Origins in the Genus Drosophila Genetics, November 1, 2007; 177(3): 1291 - 1301. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. Park, D. M. MacAlpine, and T. L. Orr-Weaver Inaugural Article: Drosophila follicle cell amplicons as models for metazoan DNA replication: A cyclinE mutant exhibits increased replication fork elongation PNAS, October 23, 2007; 104(43): 16739 - 16746. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Lake, K. Teeter, S. L. Page, R. Nielsen, and R. S. Hawley A Genetic Analysis of the Drosophila mcm5 Gene Defines a Domain Specifically Required for Meiotic Recombination Genetics, August 1, 2007; 176(4): 2151 - 2163. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Moyer, P. W. Lewis, and M. R. Botchan Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase PNAS, July 5, 2006; 103(27): 10236 - 10241. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Ryu, J. Holzschuh, S. Erhardt, A.-K. Ettl, and W. Driever Depletion of minichromosome maintenance protein 5 in the zebrafish retina causes cell-cycle defect and apoptosis PNAS, December 20, 2005; 102(51): 18467 - 18472. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. R. May, M. Thomer, K. F. Murnen, and B. R. Calvi Levels of the origin-binding protein Double parked and its inhibitor Geminin increase in response to replication stress J. Cell Sci., September 15, 2005; 118(18): 4207 - 4217. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Thomer, N. R. May, B. D. Aggarwal, G. Kwok, and B. R. Calvi Drosophila double-parked is sufficient to induce re-replication during development and is regulated by cyclin E/CDK2 Development, October 1, 2004; 131(19): 4807 - 4818. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. L. Beall, M. Bell, D. Georlette, and M. R. Botchan Dm-myb mutant lethality in Drosophila is dependent upon mip130: positive and negative regulation of DNA replication Genes & Dev., July 15, 2004; 18(14): 1667 - 1680. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Zhang and J. Tower Sequence requirements for function of the Drosophila chorion gene locus ACE3 replicator and ori-{beta} origin elements Development, May 1, 2004; 131(9): 2089 - 2099. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Cayirlioglu, W. O. Ward, S. C. Silver Key, and R. J. Duronio Transcriptional Repressor Functions of Drosophila E2F1 and E2F2 Cooperate To Inhibit Genomic DNA Synthesis in Ovarian Follicle Cells Mol. Cell. Biol., March 15, 2003; 23(6): 2123 - 2134. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. V. Lunyak, M. Ezrokhi, H. S. Smith, and S. A. Gerbi Developmental Changes in the Sciara II/9A Initiation Zone for DNA Replication Mol. Cell. Biol., December 15, 2002; 22(24): 8426 - 8437. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. M. Claycomb, D. M. MacAlpine, J. G. Evans, S. P. Bell, and T. L. Orr-Weaver Visualization of replication initiation and elongation in Drosophila J. Cell Biol., October 28, 2002; 159(2): 225 - 236. [Abstract] [Full Text] [PDF] |
||||