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dc.contributor.authorIvana, Barbaric,
dc.contributor.authorPeter W, Andrews,
dc.contributor.authorHalliwell, J.A.
dc.contributor.authorFrith, T.J.R.
dc.contributor.authorLaing, O.
dc.contributor.authorPrice, C.J.
dc.contributor.authorBower, O.J.
dc.contributor.authorStavish, T.
dc.contributor.authorGokhale, P.J.
dc.contributor.authorHewitt, Z.
dc.contributor.authorEl-Khamisy, Sherif
dc.date.accessioned2020-08-25T15:24:20Z
dc.date.accessioned2020-09-16T10:43:21Z
dc.date.available2020-08-25T15:24:20Z
dc.date.available2020-09-16T10:43:21Z
dc.date.issued2020-06-09
dc.identifier.citationHalliwell JA, Frith TJR, Laing O et al (2020) Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells. Stem Cell Reports. 14(6): 1009-1017.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18013
dc.descriptionYesen_US
dc.description.abstractHuman pluripotent stem cells (PSCs) are subject to the appearance of recurrent genetic variants on prolonged culture. We have now found that, compared with isogenic differentiated cells, PSCs exhibit evidence of considerably more DNA damage during the S phase of the cell cycle, apparently as a consequence of DNA replication stress marked by slower progression of DNA replication, activation of latent origins of replication, and collapse of replication forks. As in many cancers, which, like PSCs, exhibit a shortened G1 phase and DNA replication stress, the resulting DNA damage may underlie the higher incidence of abnormal and abortive mitoses in PSCs, resulting in chromosomal non-dysjunction or cell death. However, we have found that the extent of DNA replication stress, DNA damage, and consequent aberrant mitoses can be substantially reduced by culturing PSCs in the presence of exogenous nucleosides, resulting in improved survival, clonogenicity, and population growth.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.stemcr.2020.04.004en_US
dc.rights(c) 2020 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectPluripotenten_US
dc.subjectDNAen_US
dc.subjectDamageen_US
dc.subjectReplicationen_US
dc.subjectStressen_US
dc.subjectNucleosidesen_US
dc.subjectMitoticen_US
dc.subjectErrorsen_US
dc.subjectHumanen_US
dc.titleNucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cellsen_US
dc.status.refereedYesen_US
dc.date.Accepted2020-04-14
dc.date.application2020-05-14
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.date.updated2020-08-25T14:24:28Z
refterms.dateFOA2020-09-16T10:43:52Z


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