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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/30989
Title: Replication-independent endogenous DNA double-strand breaks in saccharomyces cerevisiae model
Authors: Jirapan Thongsroy
Oranart Matangkasombut
Araya Thongnak
Prakasit Rattanatanyong
Siwanon Jirawatnotai
Apiwat Mutirangura
Chulalongkorn University
Harvard Medical School
Mahidol University
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 19-Aug-2013
Citation: PLoS ONE. Vol.8, No.8 (2013)
Abstract: © 2013 Thongsroy et al. Without exposure to any DNA-damaging agents, non-dividing eukaryotic cells carry endogenous DNA double-strand breaks (EDSBs), or Replication-Independent (RIND)-EDSBs. In human cells, RIND-EDSBs are enriched in the methylated heterochromatic areas of the genome and are repaired by an ATM-dependent non-homologous end-joining pathway (NHEJ). Here, we showed that Saccharomyces cerevisiae similarly possess RIND-EDSBs. Various levels of EDSBs were detected during different phases of the cell cycle, including G0. Using a collection of mutant yeast strains, we investigated various DNA metabolic and DNA repair pathways that might be involved in the maintenance of RIND-EDSB levels. We found that the RIND-EDSB levels increased significantly in yeast strains lacking proteins involved in NHEJ DNA repair and in suppression of heterochromatin formation. RIND-EDSB levels were also upregulated when genes encoding histone deacetylase, endonucleases, topoisomerase, and DNA repair regulators were deleted. In contrast, RIND-EDSB levels were downregulated in the mutants that lack chromatin-condensing proteins, such as the high-mobility group box proteins, and Sir2. Likewise, RIND-EDSB levels were also decreased in human cells lacking HMGB1. Therefore, we conclude that the genomic levels of RIND-EDSBs are evolutionally conserved, dynamically regulated, and may be influenced by genome topology, chromatin structure, and the efficiency of DNA repair systems.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84906836118&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/30989
ISSN: 19326203
Appears in Collections:Scopus 2011-2015

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