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Article: Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels

TitleLoss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels
Authors
Issue Date2009
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
Plos Genetics, 2009, v. 5 n. 10 How to Cite?
AbstractPeroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Δ cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Δ cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Δ cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability. © 2009 Tang et al.
Persistent Identifierhttp://hdl.handle.net/10722/124514
ISSN
2014 Impact Factor: 7.528
2015 SCImago Journal Rankings: 6.308
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7340/03M
HKU7670/07M
Funding Information:

This work is supported by Hong Kong Research Grants Council (projects HKU7340/03M and HKU7670/07M). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorTang, HMVen_HK
dc.contributor.authorSiu, KLen_HK
dc.contributor.authorWong, CMen_HK
dc.contributor.authorJin, DYen_HK
dc.date.accessioned2010-10-31T10:38:43Z-
dc.date.available2010-10-31T10:38:43Z-
dc.date.issued2009en_HK
dc.identifier.citationPlos Genetics, 2009, v. 5 n. 10en_HK
dc.identifier.issn1553-7390en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124514-
dc.description.abstractPeroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Δ cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Δ cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Δ cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability. © 2009 Tang et al.en_HK
dc.languageengen_HK
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_HK
dc.relation.ispartofPLoS Geneticsen_HK
dc.subject.meshDNA Damage-
dc.subject.meshGenomic Instability-
dc.subject.meshNucleotides - metabolism-
dc.subject.meshPeroxidases - genetics - metabolism-
dc.subject.meshSaccharomyces cerevisiae - genetics - metabolism-
dc.titleLoss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levelsen_HK
dc.typeArticleen_HK
dc.identifier.emailWong, CM:wispwong@hkucc.hku.hken_HK
dc.identifier.emailJin, DY:dyjin@hkucc.hku.hken_HK
dc.identifier.authorityWong, CM=rp01489en_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pgen.1000697en_HK
dc.identifier.pmid19851444-
dc.identifier.pmcidPMC2758587-
dc.identifier.scopuseid_2-s2.0-73449116050en_HK
dc.identifier.hkuros175810en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73449116050&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume5en_HK
dc.identifier.issue10en_HK
dc.identifier.spagee1000697en_HK
dc.identifier.eissn1553-7404-
dc.identifier.isiWOS:000272032100035-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, HMV=35328375400en_HK
dc.identifier.scopusauthoridSiu, KL=7102312040en_HK
dc.identifier.scopusauthoridWong, CM=18134632400en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK

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