Spelling suggestions: "subject:"microhomologymediated dnd joining"" "subject:"microhomologymediated dnd coining""
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A Regulatory Role for ATM in Suppression of Mre11-Dependent DNA Degradation and Microhomology-Mediated End JoiningRahal, Elias Adel January 2009 (has links)
ATM is the defective kinase in the neurodegenerative disorder ataxia telangiectasia. This kinase is associated with DNA double-strand break (DSB) repair and cell cycle control. Our laboratory previously demonstrated elevated levels of deletions and error-prone double-strand break repair via microhomology-mediated end joining (MMEJ) in ATM-deficient (A-T) extracts when compared to controls (wtATM+). To assess the involvement of enhanced nuclease activities in A-T extracts we studied the stability of DNA duplex substrates in A-T and control nuclear extracts under DSB repair conditions. We observed a marked shift in detection from full-length products to shorter products in A-T extracts. Addition of purified ATM to A-T nuclear extracts restored full-length product detection. This repression of degradation by ATM was dependent on its kinase activities. These results demonstrated a role for ATM in suppressing the degradation of DNA ends possibly through inhibiting nucleases implicated in MMEJ such as Mre11. Therefore, we assessed DNA end-stability in Mre11-depleted nuclear extracts and in extracts treated with the Mre11 nuclease inhibitor, Mirin. This resulted in decreased DNA degradation in both control and A-T extracts. Knockdown of Mre11 levels also led to an enhancement of DNA end-stability in nuclear extracts. Examining MMEJ levels by employing an in vivo reporter assay system revealed a decline in this pathway in Mre11-knockdown cells and in those treated with Mirin. These results signify a role for the Mre11 nuclease in MMEJ in mammalian cells and indicate a regulatory function for ATM in the control of error-prone DSB repair and preservation of DNA end-stability at a break.
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Double-Strand DNA Break Repair By Homologous Recombination Contributes To The Preservation of Genomic Stability In Mouse Embryonic Stem CellsTichy, Elisia D. 13 April 2010 (has links)
No description available.
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Genome-wide microhomologies enable precise template-free editing of biologically relevant deletion mutations / ゲノムワイドなマイクロホモロジーを活用した正確かつテンプレートフリーなヒト欠失変異のゲノム編集技術の開発Janin, Grajcarek 23 March 2020 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医科学) / 甲第22379号 / 医科博第109号 / 新制||医科||7(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 遊佐 宏介, 教授 武田 俊一, 教授 近藤 玄 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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