Investigating the mechanisms of DNA repair in C. elegans
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Date
2021
Authors
Lo, Julia
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Meiosis is a specialized cell division that separates homologous chromosomes to generate haploid sperm and egg cells. During meiosis, segregation of homologous chromosomes requires induction and repair of DNA double strand breaks (DSBs) via recombination. Without DSBs, improper segregation can lead to genetic disorders, cancers, and infertility. Methylation of histones, proteins organizing DNA as dense heterochromatin or loose euchromatin, change aspects of chromosome function during meiosis. Notably, it is not understood how histone modifications and changes in chromatin state affect fidelity of DSB induction and repair. One hypothesis is the open nature of euchromatin promotes DSB induction and repair with higher fidelity. MET-2 histone methyltransferase causes accumulation of H3K9 dimethylation (H3K9me2), a heterochromatic mark, in the C. elegans germline. I explore how global changes in histone methylation affect quantity of DSBs in the C. elegans germline using immunofluorescence for this mark and DSBs in met-2 null mutants lacking H3K9me2. I showed how the presence of a specific chromatin mark affects the DSB repair program in early and late meiosis. My experiments indicate met-2 mutants induce fewer DSBs in early meiosis than wild type. Yet, in late meiosis, when breaks are repaired, met-2 and wild type have the same average number of DSBs per nucleus. This suggests that H3K9 dimethylation is playing a greater role in regulating the efficient induction of DSBs.
Description
1 page.
Keywords
meiosis, C. elegans, DNA damage, double strand break