A Novel Transcription-Interference Mechanism To Suppress Checkpoint
thesisposted on 23.05.2021, 17:39 by Liza Marie Hayley Calhoun
Meiosis is a linear differentiation pathway remarkable for deliberate DNA damage. During meiotic prophase, DNA damage checkpoint is repressed, which may promote homologous recombination and repair. Meiotic breaks are known to influence meiotic chromosome segregation, preventing aneuploidy in gametes. Convergent genes cause transcriptional interference through overlapping transcripts, resulting in gene suppression. This general mechanism of gene silencing has been noted in both yeast and metazoans. In Schizosaccharomyces pombe, chk1⁺ is convergent with the meiotically upregulated meu27⁺ gene. Through gain- and loss-of-function assays we are developing a model of checkpoint regulation during nitrogen stress. We find that altered meu27⁺ expression impacts chk1⁺ mRNA levels, DNA segregation, and cell cycle progression. S. pombe encodes several DNA damage checkpoint genes that are convergent with stress-inducible transcripts. Therefore, we investigate the possibility that convergent transcription is a mechanism altering DNA damage repair during other stresses and differentiation programmes which may trigger unregulated cell division.