Discovery and identification of genes involved in DNA damage repair in yeast.

Autor: Jagadeesan SK; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: sasikumarjagadeesan@cmail.carleton.ca., Potter T; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: taylorpotter@cmail.carleton.ca., Al-Gafari M; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: mustafaalgafari@cmail.carleton.ca., Hooshyar M; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: mohsen.hooshyar@Carleton.ca., Hewapathirana CM; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: minukahewapathirana@cmail.carleton.ca., Takallou S; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: saratakalloo@cmail.carleton.ca., Hajikarimlou M; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: maryamhajikarimlou@cmail.carleton.ca., Burnside D; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: daniel.burnside@carleton.ca., Samanfar B; Agriculture and Agri-Food Canada, Ottawa Research and Development Centre (ORDC), Ottawa, Ontario, Canada. Electronic address: bahram.samanfar@canada.ca., Moteshareie H; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: houman.moteshareie@carleton.ca., Smith M; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: myronSmith@cunet.carleton.ca., Golshani A; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, Canada; Department of Biology, Carleton University, Ottawa, Ontario, Canada. Electronic address: ashkan.golshani@carleton.ca.
Jazyk: angličtina
Zdroj: Gene [Gene] 2022 Jul 15; Vol. 831, pp. 146549. Date of Electronic Publication: 2022 May 13.
DOI: 10.1016/j.gene.2022.146549
Abstrakt: DNA repair defects are common in tumour cells and can lead to misrepair of double-strand breaks (DSBs), posing a significant challenge to cellular integrity. The overall mechanisms of DSB have been known for decades. However, the list of the genes that affect the efficiency of DSB repair continues to grow. Additional factors that play a role in DSB repair pathways have yet to be identified. In this study, we present a computational approach to identify novel gene functions that are involved in DNA damage repair in Saccharomyces cerevisiae. Among the primary candidates, GAL7, YMR130W, and YHI9 were selected for further analysis since they had not previously been identified as being active in DNA repair pathways. Originally, GAL7 was linked to galactose metabolism. YHI9 and YMR130W encode proteins of unknown functions. Laboratory testing of deletion strains gal7Δ, ymr130wΔ, and yhi9Δ implicated all 3 genes in Homologous Recombination (HR) and/or Non-Homologous End Joining (NHEJ) repair pathways, and enhanced sensitivity to DNA damage-inducing drugs suggested involvement in the broader DNA damage repair machinery. A subsequent genetic interaction analysis revealed interconnections of these three genes, most strikingly through SIR2, SIR3 and SIR4 that are involved in chromatin regulation and DNA damage repair network.
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Databáze: MEDLINE