Genetic and functional analysis of PARP, a DNA strand break-binding enzyme

Area of Science:

• Molecular Biology
• Developmental Biology
• Genetics

Background:

• Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in DNA repair and apoptosis.
• PARP knockout studies suggest its role in maintaining chromosomal stability.
• Understanding PARP's function during development is crucial.

Purpose of the Study:

• To investigate the function of Poly(ADP-ribose) polymerase (PARP) during developmental stages in Drosophila melanogaster.
• To analyze the effects of PARP overexpression and loss of function.
• To explore PARP's role in cell cycle regulation and programmed cell death.

Main Methods:

• Cloning of PARP cDNA and gene from Drosophila melanogaster.
• Studying gene expression patterns using in situ mRNA hybridization.
• Generating transgenic Drosophila by P element-mediated germ line transformation to overexpress PARP.
• Analyzing developmental defects in eye discs of transgenic flies.

Main Results:

• An alternatively spliced form of PARP lacking the auto-modification domain was identified in Drosophila.
• PARP gene expression is high in early embryos and decreases over time.
• PARP mRNA localizes to the central nervous system in late-stage embryos.
• Overexpression of PARP in Drosophila eye discs resulted in tissue polarity disruption, including ommatidial missrotation and incorrect chirality.

Conclusions:

• PARP plays a significant role in Drosophila development, particularly in tissue polarity and cellular organization.
• The study provides a model for investigating PARP's involvement in cell cycle control and programmed cell death.
• Further research is needed to elucidate the precise mechanisms by which PARP influences developmental processes.