Rapid DNA replication origin licensing protects stem cell pluripotency

• DOI: 10.7554/elife.30473
• Publication Date: 2017-11-17T16:07:51Z
• Authors: Jacob Peter Matson; Raluca Dumitru; Philip Coryell; Ryan M Baxley; Weili Chen; Kirk Twaroski; Beau R Webber; Jakub Tolar; Anja-Katrin Bieli...; Jeremy E Purvis; Jeanette Gowen Cook
• Keywords: Minichromosome maintenance; DNA re-replication

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 length varies widely among types. Using quantitative single-cell analyses, we found that pluripotent stem cells with naturally short phases load MCM much faster than their isogenic differentiated counterparts long phases. During earliest stages differentiation toward all lineages, slows concurrently lengthening, revealing developmental control loading. In contrast, ectopic Cyclin E overproduction uncouples from fast Rapid licensing in caused by accumulation protein, Cdt1. Prematurely slowing not only lengthens also accelerates differentiation. Thus, rapid intrinsic characteristic contributes pluripotency maintenance.