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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18967

Title: Response of Human Hematopoietic Cells to DNA Double-strand Breaks
Authors: Trottier, Magan
Advisor: Meyn, M. Stephen
Department: Molecular and Medical Genetics
Keywords: primitive hematopoietic cell
DNA double-strand break
cell cycle
neutral comet assay
53BP1 foci
H2AX foci
Issue Date: 16-Feb-2010
Abstract: Maintenance of hematopoiesis depends upon rare hematopoietic stem cells (HSCs), which can persist over an organism’s lifetime. It is conceivable that they must maintain a high degree of genetic stability; otherwise recurring exposure to genotoxins and accumulation of genetic changes could result in genomic instability and malignancy or cell death. We have focused on the response of HSCs and primitive hematopoietic cells to highly toxic DNA double-strand breaks (DSBs). Using assays to detect break rejoining and kinetics of early DSB response foci, we determined that non-cycling human HSC-containing cells display delayed break rejoining kinetics and persistent γH2AX and 53BP1 foci compared to cycling counterparts, more differentiated hematopoietic cells and human primary fibroblasts. In contrast, when stimulated to cycle, these HSC-containing cells are quite efficient at repairing breaks and resolving foci. These data suggest that the DNA damage response may be unusually prolonged in non-cycling primitive hematopoietic cells.
URI: http://hdl.handle.net/1807/18967
Appears in Collections:Master
Department of Molecular Genetics - Master theses

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