Investigating meiotic DNA double-strand break interference in S. cerevisiae

López Ruiz, Luz María (2022) Investigating meiotic DNA double-strand break interference in S. cerevisiae. Doctoral thesis (PhD), University of Sussex.

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Abstract

Meiotic recombination is initiated by the programmed formation of DNA double-strand breaks (DSBs), however the presence of these types of lesions can easily compromise the integrity of the cell. As such, cells have developed multiple regulatory pathways to control when, how many and where DSBs are formed in order to ensure a proper timing (temporal regulation), number (quantitative regulation) and distribution (spatial regulation) of DSBs across the genome. Among the pathways involved in shaping the distribution of DSBs, Tel1-dependent DSB interference has emerged as one of the core negative feedbacks that pattern the DSB landscape. However, how Tel1-dependent DSB interference operates in space and what features are involved is poorly understood.

The work presented in this thesis uses: (i) specific techniques to study Tel1-dependent DSB interference (Chapter 3) and the influence of the chromosome structure on Tel1-dependent DSB interference using meiotic sister chromatid cohesin rec8Δ mutants (Chapter 4) at specific genomic locations; (ii) a novel method to map Spo11-DSBs genome wide (CC-seq) to study the effect that Tel1 exerts on a genome-wide scale (Chapter 5 and 6); (iii) a simulation platform that mimics the effect that DSB interference would impose over the distribution of DSBs in silico (MATLAB: DSBSim) to investigate the process of Tel1–dependent DSB interference (Chapter 6) and to explore the features—such as Tel1 kinase activity, chromosome structure and chromosome compaction—that influence such a phenomenon (Chapter 7).

Collectively, this thesis further elucidates the mechanisms underpinning the process of Tel1-dependent DSB interference and therefore contribute to our understanding of how DSBs are spatially regulated in S. cerevisiae during meiosis.

Item Type: Thesis (Doctoral)
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Depositing User: Library Cataloguing
Date Deposited: 22 Apr 2022 11:39
Last Modified: 22 Apr 2022 11:39
URI: http://sro.sussex.ac.uk/id/eprint/105460

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