Temporal Analysis of DSB Formation in Meiotic Prophase Heterochromatin. Marissa C. Pelot¹, R. Scott Hawley^1,2. 1) Stowers Institute for Medical Research, Kansas City, MO 64110; 2) Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160.

   Heterochromatin, DNA that is generally characterized as gene-poor, and enriched for repetitive sequences, has, in the past, had a reputation as junk DNA. However, it is now known to play important roles in a number of biological processes. Because heterochromatin is highly enriched for repetitive sequences, the repair of double-strand DNA breaks (DSBs) within it presents a special challenge. Imprecise repair of DSBs in highly repetitive regions could result in the loss or gain of DNA or formation of aberrant chromosomes. These aberrant products can contribute to cancer and other human diseases. In somatic cells, DSBs only occur in response to damage, such as that done by ionizing radiation (IR). In meiosis, however, cells enter a program that incorporates DSB formation as a necessary prerequisite for synapsis and recombination. DSBs are not formed in heterochromatin as part of the normal meiotic program, but meiotic heterochromatin is not refractory to DSBs induced by IR. Little is known regarding the kinetics or the resolution DSBs induced this way. Using Drosophila oocytes as a model, we have examined the kinetics of DSB formation induced by IR in early meiotic prophase, with surprising results. Preliminary data indicates a delay in the recognition of DSBs in meiotic heterochromatin compared to those formed in mitotic heterochromatin. DSBs in meiotic heterochromatin also interact with components of recombination machinery, though the mechanism for their resolution remains to be investigated. These studies may further elucidate the role of heterochromatin and DSB formation in human cancers.