Epigenetic Telomere Protection by Drosophila DNA Damage Response Pathways: A Dissertation
Authors
Oikemus, Sarah R.Faculty Advisor
Michael BrodskyAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Molecular, Cell and Cancer BiologyDocument Type
Doctoral DissertationPublication Date
2006-09-08Keywords
DNA DamageDNA Repair
Epigenesis
Genetic
Drosophila Proteins
Telomere-Binding Proteins
Chromosomal Proteins
Non-Histone
DNA-Binding Proteins
Amino Acids, Peptides, and Proteins
Animal Experimentation and Research
Genetic Phenomena
Metadata
Show full item recordAbstract
Several aspects of Drosophila telomere biology indicate that telomere protection can be regulated by an epigenetic mechanism. First, terminally deleted chromosomes can be stably inherited and do not induce damage responses such as apoptosis or cell cycle arrest. Second, the telomere protection proteins HP1 and HOAP localize normally to these chromosomes and protect them from fusions. Third, unprotected telomeres still contain HeT-A sequences at sites of fusions. Taken together these observations support a model in which an epigenetic mechanism mediated by DNA damage response proteins protects Drosophilatelomeres from fusion. Work presented in this thesis demonstrates that the Drosophila proteins ATM and Nbs are required for the regulation of DNA damage responses similar to their yeast and mammalian counterparts. This work also establishes a role for the ATM and ATR DNA damage response pathways in the protection of both normal and terminally deleted chromosomes. Mutations that disrupt both pathways result in a severe telomere fusion phenotype, similar to HP1 and HOAP mutants. Consistent with this phenotype, HOAP localization at atm,atr double mutant telomeres is completely eliminated. Furthermore, telomeric sequences are still present, even at the sites of fusions. These results support a model in which an epigenetic mechanism mediated by DNA damage response proteins protects Drosophila telomeres from fusion.DOI
10.13028/034c-1d24Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31535Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/034c-1d24
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