Robert Malone

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Robert Malone
Professor Emeritus
Education:
PhD, University of Oregon, 1976
Email: Phone:
(319) 335-1112
Lab Phone:
(319) 335-1095
Office:
312 Biology Building
129 East Jefferson St., Iowa City, IA 52242-1324
Google Scholar Link:

Research Summary

Chromosome behavior in meiosis

Chromosomes undergo several special events during meiosis, the process wherein chromosome number is reduced from diploid to haploid ( to form sperm, pollen, eggs, spores, etc.). The first unique chromosomal event is genetic recombination and homologous chromosome pairing. The second unique event, the reductional division, segregates the two paired homologous chromosomes to opposite poles. We are answering three major questions about chromosomes in meiosis utilizing genetics, molecular biology, microscopy, and protein biochemistry.

First, we are asking how meiotic recombination initiates. Specifically, we are asking how the 10-12 gene products required interact with each other to form an initiation complex; in concept this complex is analogous to the complexes that initiate DNA replication. We have begun to define interactions between proteins that are only made in meiosis, and whose only role is to initiate recombination by making breaks.

Second, in collaboration with John Logsdon's group, we are asking if meiotic functions involved in recombination and the reductional division present in other organisms have conserved functions. Logsdon's analysis strongly suggests that meiosis evolved very early during the evolution of eukaryotes, perhaps simultaneously. The conclusion would be strengthened by finding that genes in other eukaryotes had retained function. We have devised expression vectors and assay systems to detect meiotic function of conserved genes that are sensitive over a 200 fold range.

Third, we have discovered that the initiation of recombination somehow signals the reductional division so that it delays until the proper time. This communication is an intracellular signal transduction process. We have determined that 8 of the 10 initiation genes are required for this signal. In addition, 2 genes involved in the special meiotic recombination structure, the synaptonemal complex, are also required for the normal delay. We are now asking how the cell detects the initiation signal, if their assembly on the chromatin is the signal, and how the signal is transduced to create the proper delay of the division. We have identified one of the targets of the signal, a major transcriptional regulator of middle meiotic genes. We are also looking for mutants that cannot carry out the proper communication between recombination initiation and the first division, in order to define the components involved in the event.

Keywords: Chromosomes, DNA, recombination, replication, segregation.

Selected Images

Technique to monitor timing of first division. Nuclei are stained with the DNA specific dye, DAPI, and monitored in the fluorescence microscope.
NDT80 is a transcription activator of the genes required for the first division. It is expressed earlier in recombination initiation mutants with an earlier division (red arrows). The gene SPS4 is a middle meiotic gene we use as a reporter; it's transcription is dependent upon active NDT80; SPS4 is expressed earlier in the mutants with an early division red arrows). White arrows show timing of wild type cells.
Pds1 degradation in rec104 initiation mutants. Cells without recombination initiation functions can undergo the first division of chromosomes without degrading the cohesions holding sisters together. A) Types of Pds1p staining in cells with one MI spindle and separated chromosomes. X axis refers to Pds1-HA staining. B) Examples of cells representing various classes. I=Pds1p degraded. II=Pds1p present in both nuclei and along spindle "1 mass".