期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2007
卷号：104
期号：43
页码：16739-16746
DOI：10.1073/pnas.0707804104
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Gene clusters amplified in the ovarian follicle cells of Drosophila serve as powerful models for metazoan DNA replication. In response to developmental signals, specific genomic regions undergo amplification by repeated firing of replication origins and bidirectional movement of replication forks for {approx}50 kb in each direction. Previous work focused on initiation of amplification, defining replication origins, establishing the role of the prereplication complex and origin recognition complex (ORC), and uncovering regulatory functions for the Myb, E2F1, and Rb transcription factors. Here, we exploit follicle cell amplification to investigate the control of DNA replication fork progression and termination, poorly understood processes in metazoans. We identified a mutant in which, during gene amplification, the replication forks move twice as far from the origin compared with wild type. This phenotype is the result of an amino acid substitution mutation in the cyclinE gene, cyclinE1f36. The rate of oogenesis is normal in cyclinE1f36/cyclinEPz8 mutant ovaries, indicating that increased replication fork progression is due to increased replication fork speed, possibly from increased processivity. The increased amplification domains observed in the mutant imply that there are not replication fork barriers preventing replication forks from progressing beyond the normal 100-kb amplified region. These results reveal a previously unrecognized role for CyclinE in controlling replication fork movement.
