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Biomedical subjects

P J Follette

Publications and source records attributed to P J Follette.

6 recordsLinked to original sources
PubMed1998

Fluctuations in cyclin E levels are required for multiple rounds of endocycle S phase in Drosophila.

The precise cell-cycle alternation of S phase and mitosis is controlled by alternating competence of nuclei to respond to S-phase-inducing factors [1]. Nuclei acquire competence to replicate at the low point in cyclin-dependent kinase (Cdk) activities that follows mitotic destruction of cyclins. The elevation of Cdk activity late in G1 is thought to drive cells into S phase and to block replicated DNA from re-acquiring replication competence [2]. Whereas mitosis is normally required to eliminate the cyclins prior to another cycle of replication, experimental elimination of Cdk activity in G2 can restore competence to replicate [3-6]. Here, we examine the roles of Cdks in the endocycies of Drosophila [7]. In these cycles, rounds of discrete S phases without intervening mitoses result in polyteny. Cyclins A and B are lost in cells as they enter endocycles [8,9], and pulses of Cyclin E expression drive endocycle S phases [10-12]. To address whether oscillations of Cyclin E expression are required for endocycles, we expressed Cyclin E continuously in Drosophila salivary glands. Growth of the cells was severely inhibited, and a period of DNA replication was induced but further replication was inhibited. This replication inhibition could be overcome by the kinase inhibitor 6-dimethylaminopurine (6-DMAP), but not by expression of subunits of the transcription factor E2F. These results indicate that endocycle S phases require oscillations in Cdk activity, but, in contrast to oscillations in mitotic cells, these occur independently of mitosis.

Animals↗
PubMed1997

Cdks and the Drosophila cell cycle.

Cyclin-dependent kinases play essential roles in driving the cell cycle. Much progress has been made in Drosophila over the past year in identifying the specific requirements for individual cyclins in particular cell cycle events. These studies encompass many aspects of the cell cycle, from the addition of a G1 phase to the cell cycle during embryogenesis to the role of cyclin degradation in progression through anaphase.

Animals↗
PubMed1995

Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant.

The yeast MCM2, MCM3, and MCM5/CDC46 genes are required for DNA replication and have been proposed to act as factors that license the DNA for one and only one round of replication per cell cycle. We have identified a Drosophila gene, DmMCM2, that is highly homologous to MCM2. A P-element insertion into this gene, which prevents its transcription, inhibits proliferation of cells in the imaginal discs and central nervous system (CNS) and causes an apparent prolongation of S phase in the embryonic and larval CNS. DmMCM2 is expressed in the embryo in a pattern corresponding to that of S-phase cells. These results suggest that DmMCM2 plays a role in the regulation of DNA replication analogous to that of its yeast counterpart.

Amino Acid Sequence↗
PubMed1992

Estimating the stability of the proposed imprinted state of the fragile-X mutation when transmitted by females.

Fragile-X syndrome is a major cause of mental retardation in humans. The X-inactivation imprinting model accounts for the unusual pattern of inheritance and expression of this syndrome. According to this model, the fragile-X mutation creates a local block to the attempted reactivation of the mutant X chromosome prior to oogenesis. This local block results in an "imprinted" fragile-X chromosome that is deleterious in males and in females for whom this chromosome is predominantly the active X chromosome. The imprinted state of the fragile-X mutation is inferred to be stable when transmitted by an imprinted female because the penetrance of the syndrome in sons of affected females is estimated to be 1.0. To provide a more precise estimate of the stability of the proposed fragile-X imprint, we have analyzed published pedigrees that include restriction fragment length polymorphism and cytogenetic data from sibships with mothers who are interpreted as having an imprinted fragile-X allele. We conclude that the fragile-X imprint was stable in 46 out of 48 female meioses. This analysis leads to a preliminary estimate of about 96% for the stability of the imprint through female meiosis. Two imprinted females had progeny who appeared to be carriers of a nonimprinted fragile-X allele. If this interpretation is correct, then reversion from the imprinted to the nonimprinted state, or "erasure," can occasionally occur when the mutant fragile-X allele is transmitted by an imprinted female. We discuss the genetic and epigenetic significance of possible female erasure. We request DNA and cytogenetic information from unpublished pedigrees to quantify further the stability, during female meiosis, of the proposed imprinted state of the mutant fragile-X allele.

Female↗