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- W3160983506 abstract "Abstract Haploid human embryonic stem cells (ESCs) provide a powerful genetic system but diploidize at high rates. We hypothesized that diploidization results from aberrant DNA replication. To test this, we profiled DNA replication timing in isogenic haploid and diploid ESCs. The greatest difference was the earlier replication of the X chromosome in haploids, consistent with the lack of X chromosome inactivation. Surprisingly, we also identified 21 autosomal regions that had dramatically delayed replication in haploids, extending beyond the normal S phase and into G2/M. Haploid-delays comprised a unique set of quiescent genomic regions that are also under-replicated in polyploid placental cells. The same delays were observed in female ESCs with two active X chromosomes, suggesting that increased X chromosome dosage may cause delayed autosomal replication. We propose that incomplete replication at the onset of mitosis could prevent cell division and result in re-entry into the cell cycle and whole genome duplication. Highlights DNA replication timing of haploid ESCs profiled by WGS Extreme replication timing delays in haploid ESCs at unique genomic regions Replication delays associate with X-chromosome dosage in multiple systems Replication delayed regions correspond to underreplication in mouse polyploid cells" @default.
- W3160983506 created "2021-05-24" @default.
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- W3160983506 date "2021-05-12" @default.
- W3160983506 modified "2023-10-18" @default.
- W3160983506 title "Delayed DNA replication in haploid human embryonic stem cells" @default.
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- W3160983506 doi "https://doi.org/10.1101/2021.05.11.443666" @default.
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