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Ablating ATR in mouse meiosis and its consequences for synapsis, recombination and meiotic surveillance mechanisms

Widger, Alexander David; (2018) Ablating ATR in mouse meiosis and its consequences for synapsis, recombination and meiotic surveillance mechanisms. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Meiosis is a fundamental part in the life cycle of sexual species. It denotes a specialised cell division that halves chromosome numbers to generate haploid gametes for reproduction. Cells unable to competently progress through meiotic prophase activate cell surveillance mechanisms causing their elimination. Given the importance of DNA damage kinases like ATR in facilitating mitotic cell surveillance mechanisms, I characterized Atr-deficient spermatocytes to determine the importance of ATR for mammalian meiosis. I found that ATR ensures efficient chromosome synapsis, and that that is partially independent of meiotic recombination. In addition, ATR has three distinct roles in meiotic recombination. Firstly, during nucleolytic processing, it acts to regulate SPO11-oligonucleotide size when ATM is deleted. Secondly, it is required for accurate RAD51 and DMC1 recruitment to DSBs. Thirdly, it regulates the timing of DNA DSB repair on both unsynapsed and synapsed chromosomes. Finally I found that the loss of ATR is unable to rescue meiotic arrest in multiple meiotic mutants, including mice deficient for the other DNA damage PIKKs ATM and DNA-PK. My findings reveal multiple roles for ATR in male mouse meiosis.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Ablating ATR in mouse meiosis and its consequences for synapsis, recombination and meiotic surveillance mechanisms
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10043772
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