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R Scott Hawley

Publications and source records attributed to R Scott Hawley.

25 records · Page 2Linked to original sources
PubMed2003

The spindle-associated transmembrane protein Axs identifies a membranous structure ensheathing the meiotic spindle.

Mutations in the aberrant X segragation (Axs) gene disrupt the segregation of achiasmate chromosomes during female meiosis in Drosophila melanogaster. We show that Axs encodes the founding member of an eukaryotic family of transmembrane proteins. Axs protein colocalizes with components of the endoplasmic reticulum and is present within a structure ensheathing the meiotic spindle. In both meiotic and mitotic cells, Axs is recruited to the microtubules of assembling spindles. We propose that Axs and the sheath represent novel mediators of meiotic spindle assembly and chromosome segregation.

Animals↗
PubMed2003

Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR.

ATM/ATR kinases act as signal transducers in eukaryotic DNA damage and replication checkpoints. Mutations in ATM/ATR homologs have pleiotropic effects that range from sterility to increased killing by genotoxins in humans, mice, and Drosophila. Here we report the generation of a null allele of mei-41, Drosophila ATM/ATR homolog, and the use of it to document a semidominant effect on a larval mitotic checkpoint and methyl methanesulfonate (MMS) sensitivity. We also tested the role of mei-41 in a recently characterized checkpoint that delays metaphase/anaphase transition after DNA damage in cellular embryos. We then compare five existing mei-41 alleles to the null with respect to known phenotypes (female sterility, cell cycle checkpoints, and MMS resistance). We find that not all phenotypes are affected equally by each allele, i.e., the functions of MEI-41 in ensuring fertility, cell cycle regulation, and resistance to genotoxins are genetically separable. We propose that MEI-41 acts not in a single rigid signal transduction pathway, but in multiple molecular contexts to carry out its many functions. Sequence analysis identified mutations, which, for most alleles, fall in the poorly characterized region outside the kinase domain; this allowed us to tentatively identify additional functional domains of MEI-41 that could be subjected to future structure-function studies of this key molecule.

Alleles↗
PubMed2003

A deficiency screen of the major autosomes identifies a gene (matrimony) that is haplo-insufficient for achiasmate segregation in Drosophila oocytes.

In Drosophila oocytes, euchromatic homolog-homolog associations are released at the end of pachytene, while heterochromatic pairings persist until metaphase I. A screen of 123 autosomal deficiencies for dominant effects on achiasmate chromosome segregation has identified a single gene that is haplo-insufficient for homologous achiasmate segregation and whose product may be required for the maintenance of such heterochromatic pairings. Of the deficiencies tested, only one exhibited a strong dominant effect on achiasmate segregation, inducing both X and fourth chromosome nondisjunction in FM7/X females. Five overlapping deficiencies showed a similar dominant effect on achiasmate chromosome disjunction and mapped the haplo-insufficient meiotic gene to a small interval within 66C7-12. A P-element insertion mutation in this interval exhibits a similar dominant effect on achiasmate segregation, inducing both high levels of X and fourth chromosome nondisjunction in FM7/X females and high levels of fourth chromosome nondisjunction in X/X females. The insertion site for this P element lies immediately upstream of CG18543, and germline expression of a UAS-CG18543 cDNA construct driven by nanos-GAL4 fully rescues the dominant meiotic defect. We conclude that CG18543 is the haplo-insufficient gene and have renamed this gene matrimony (mtrm). Cytological studies of prometaphase and metaphase I in mtrm hemizygotes demonstrate that achiasmate chromosomes are not properly positioned with respect to their homolog on the meiotic spindle. One possible, albeit speculative, interpretation of these data is that the presence of only a single copy of mtrm disrupts the function of whatever "glue" holds heterochromatically paired homologs together from the end of pachytene until metaphase I.

Animals↗
PubMed2002

Meiosis: how male flies do meiosis.

In meiosis in male fruitflies, chromosome pairing events do not facilitate genetic exchange, but rather create bivalents that can be sequestered to discrete pockets of the prophase nucleus. This assignment of homologs to a common pocket likely facilitates the orientation of homologous centromeres to opposite poles.

Anaphase↗
PubMed2002

Playing for half the deck: the molecular biology of meiosis.

Meiosis reduces the number of chromosomes carried by a diploid organism by half, partitioning precisely one haploid genome into each gamete. The basic events of meiosis reflect three meiosis-specific processes: first, pairing and synapsis of homologous chromosomes; second, high-frequency, precisely controlled, reciprocal crossover; third, the regulation of sister-chromatid cohesion (SCC), such that during anaphase I, SCC is released along the chromosome arms, but not at the centromeres. The failure of any of these processes can result in aneuploidy or a failure of meiotic segregation.

Animals↗