• campus:  a to z index
• map
• directory
• calendar

Search:

Kent Golic

Professor of Biology

 

Research

References

 

 

Research

My laboratory studies the relationship between chromosome structure and function. We use the fruit fly Drosophila melanogaster because of the powerful combination of excellent genetics and chromosome cytology that is available with this organism. We have two primary areas of interest.

1. Telomeres are special nucleic acid/protein structures found at the ends of linear chromosomes in eukaryotes, and are necessary for maintaining chromosome integrity. The regulation of telomere maintenance may play a role in aging, and malfunctions of this regulation are very frequently associated with cancer. We are interested in telomere function and in how cells respond to loss of a telomere. We developed a system to cause the loss of a single telomere during development. Inducible site-specific recombination mediates the formation of a dicentric chromosome that is completely dispensable. The dicentric then breaks during mitosis to deliver a single non-telomeric chromosome end to the two daughter cells. Our initial investigations revealed that somatic cells experience cell cycle arrest and apoptosis in response to this broken end. These responses are highly similar to the responses of mammalian cells to telomere loss. In male germline cells, however, new telomeres are efficiently constructed on broken ends and these "healed" chromosomes are transmissible. We are working to understand the role of the DNA damage and repair machinery and the cell cycle regulatory system in the somatic and germline responses. We are particularly interested in how cells of the male germline choose to build a new telomere on a broken chromosome end, and in the nature of the telomeres that are formed on the broken chromosome fragments.

2. Genomic imprinting is the term applied to certain examples of non-Mendelian inheritance, in which chromosomes or regions of chromosomes are marked by a parent, so that in their offspring maternal and paternal genetic material is treated differently. We have found that the heterochromatin of the X and Y chromosomes of Drosophila melanogaster is subject to imprinting, and that reporter genes inserted into these regions of the sex chromosomes show differential expression that is determined by the sex of the parent from which it was inherited. The aim of our current work is to elucidate the mechanism by which the paternal and maternal chromosomes are differentially marked. Chromatin structure is a prime candidate for this regulation, as is DNA methylation. Ultimately, we would like to understand the role for imprinting in Drosophila.

Embryonic mitoses exhibiting anaphase bridges and broken chromosomes resulting from dicentric chromosome formation.

The influence of imprinting on gene expression. The abdomens of two genetically identical females are shown. Each carries a yellow + reporter gene inserted into sex chromosome heterochromatin. Expression of this gene produces the dark stripes found at the posterior of each abdominal segment. The female on the left inherited yellow + maternally and shows almost complete expression of the gene. The female on the right inherited the same gene paternally and shows expression in only a few scattered cells.

References