Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality.

ABSTRACT: Replicative stress during embryonic development influences ageing and predisposition to disease in adults. A protective mechanism against replicative stress is provided by the licensing of thousands of origins in G1 that are not necessarily activated in the subsequent S-phase. These 'dormant' origins provide a backup in the presence of stalled forks and may confer flexibility to the replication program in specific cell types during differentiation, a role that has remained unexplored. Here we show, using a mouse strain with hypomorphic expression of the origin licensing factor mini-chromosome maintenance (MCM)3 that limiting origin licensing in vivo affects the functionality of hematopoietic stem cells and the differentiation of rapidly-dividing erythrocyte precursors. Mcm3-deficient eryth

SUBMITTER: Alvarez S 

PROVIDER: S-EPMC4608254 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature