Nucleosides Rescue Replication-Mediated Genome Instability of Human Pluripotent Stem Cells.

ABSTRACT: Human 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 cons

SUBMITTER: Halliwell JA 

PROVIDER: S-EPMC7355123 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature