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dc.contributor.authorRollins, MaryClare F.
dc.contributor.authorvan der Heide, Dana M.
dc.contributor.authorWeisend, Carla M.
dc.contributor.authorKundert, Jean A.
dc.contributor.authorComstock, Kristin M.
dc.contributor.authorSuvorova, Elena S.
dc.contributor.authorCapecchi, Mario R.
dc.contributor.authorMerrill, Gary F.
dc.contributor.authorSchmidt, Edward E.
dc.date.accessioned2019-04-17T20:57:09Z
dc.date.available2019-04-17T20:57:09Z
dc.date.issued2010-07
dc.identifier.citationRollins, MaryClare F., Dana M. van der Heide, Carla M. Weisend, Jean A. Kundert, Kristin M. Comstock, Elena S. Suvorova, Mario R. Capecchi, Gary F. Merrill, and Edward E. Schmidt. “Hepatocytes Lacking Thioredoxin Reductase 1 Have Normal Replicative Potential During Development and Regeneration.” Journal of Cell Science 123, no. 14 (June 22, 2010): 2402–2412. doi:10.1242/jcs.068106.en_US
dc.identifier.issn1477-9137
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/15443
dc.description.abstractCells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms. We have studied proliferation of thioredoxin-reductase-1 (Txnrd1)-deficient hepatocytes in mice. During development and regeneration, normal mice and mice having Txnrd1-deficient hepatocytes exhibited similar liver growth rates. Proportions of hepatocytes that immunostained for PCNA, phosphohistone H3 or incorporated BrdU were also similar, indicating livers of either genotype had similar levels of proliferative, S and M phase hepatocytes, respectively. Replication was blocked by hydroxyurea, confirming that RNR activity was required by Txnrd1-deficient hepatocytes. Regenerative thymidine incorporation was similar in normal and Txnrd1-deficient livers, further indicating that DNA synthesis was unaffected. Using genetic chimeras in which a fluorescently marked subset of hepatocytes was Txnrd1-deficient while others were not, we found that the multigenerational contributions of both hepatocyte types to development and to liver regeneration were indistinguishable. We conclude that, in mouse hepatocytes, a Txnrd1-independent route for the supply of electrons to RNR can fully support DNA replication and normal proliferative growth.en_US
dc.description.sponsorshipMontana State University Scholars Program; Howard Hughes Medical Institute's Undergraduate Research Program; National Science Foundation's Research Experiences for Undergraduates program; Montana Agricultural Experiment Station; NIH COBRE grant P20 RR020185; NSFen_US
dc.language.isoenen_US
dc.rightsThis Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en_US
dc.titleHepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regenerationen_US
dc.typeArticleen_US
mus.citation.extentfirstpage2402en_US
mus.citation.extentlastpage2412en_US
mus.citation.issue4en_US
mus.citation.journaltitleJournal of Cell Scienceen_US
mus.citation.volume123en_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.doi10.1242/jcs.068106en_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.relation.researchgroupMT INBRE Bioinformatics and Biostatistics Core.en_US
mus.data.thumbpage7en_US


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