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Publication

Rapid DNA replication origin licensing protects stem cell pluripotency.

eLife | 2017

Complete and robust human genome duplication requires loading minichromosome maintenance (MCM) helicase complexes at many DNA replication origins, an essential process termed origin licensing. Licensing is restricted to G1 phase of the cell cycle, but G1 length varies widely among cell types. Using quantitative single-cell analyses, we found that pluripotent stem cells with naturally short G1 phases load MCM much faster than their isogenic differentiated counterparts with long G1 phases. During the earliest stages of differentiation toward all lineages, MCM loading slows concurrently with G1 lengthening, revealing developmental control of MCM loading. In contrast, ectopic Cyclin E overproduction uncouples short G1 from fast MCM loading. Rapid licensing in stem cells is caused by accumulation of the MCM loading protein, Cdt1. Prematurely slowing MCM loading in pluripotent cells not only lengthens G1 but also accelerates differentiation. Thus, rapid origin licensing is an intrinsic characteristic of stem cells that contributes to pluripotency maintenance.

Pubmed ID: 29148972 RIS Download

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Associated grants

Agency: NIGMS NIH HHS, United States
Id: R01 GM083024
Agency: NCI NIH HHS, United States
Id: P30 CA077598
Agency: NHLBI NIH HHS, United States
Id: T32 HL007062
Agency: NIGMS NIH HHS, United States
Id: R01 GM074917
Agency: NCI NIH HHS, United States
Id: P30 CA016086
Agency: NCI NIH HHS, United States
Id: T32 CA009138
Agency: NICHD NIH HHS, United States
Id: DP2 HD091800
Agency: NIGMS NIH HHS, United States
Id: R01 GM102413

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