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Developmental and Cell Biology Seminar Series with Irene Chiolo
January 14, 2021 @ 11:00 a.m. - 12:00 p.m.Free
Highways for Repair: Nuclear Actin Filaments and Myosins Drive Relocalization and Repair of Heterochromatic DNA Breaks
Join the UCI BioSci Department of Developmental and Cell Biology in a virtual seminar with Irene Chiolo, Associate Professor of the Department of Biological Sciences of the University of Southern California.
Pericentromeric heterochromatin accounts for ~30% of fly and human genomes and is mostly composed of repeated DNA sequences prone to aberrant recombination. Defective double-strand break (DSB) repair of heterochromatin results in widespread genome instability, a major driving force for tumorigenesis. Genome instability is also a leading cause of aging-related diseases and contributes to developmental defects, sterility, and neurological and neuromuscular degeneration in several genetic syndromes. And yet, repair mechanisms in heterochromatin have been woefully understudied. Using Drosophila cells, our pioneering studies have identified a striking relocalization of repair sites to the nuclear periphery for ‘safe’ homologous recombination (HR) progression. SUMOylation has a pivotal role in this pathway, by blocking HR inside the domain and promoting relocalization. We have also uncovered a remarkable network of transient nuclear actin filaments and myosins driving directed motions to the nuclear periphery, and we have identified highly conserved pathways in mammalian cells. More recently, we have discovered a role for nucleoporins in mobilizing repair sites ‘off pore’, likely through phase separation. Ultimately, we expect these studies to open new avenues for cancer treatment and for developing more effective strategies to address aging-related disorders and neurological/neuromuscular diseases.