Origin firing articles from across Nature Portfolio

Effective and regulated activation of the Mcm2-7 helicase underlies faithful genome replication. Here the authors reveal mechanistic detail how the pre-loading complex proteins TopBP1 and GINS interact and, thus, how the helicase activator GINS loads on Mcm2-7 during replication origin firing.

Here, the authors show that a DnaA:origin complex promotes specific nucleobase capture from a single DNA strand. It is proposed that this mechanism may play a key role stimulating opening of bacterial chromosome origins.

Here the authors show that in activated B cells, RIF1 primarily binds early-replicating active chromatin and promotes early replication. RIF1 and MCM proteins establish early replication timing signatures genome-wide and ensure early replication of highly transcribed genes.

In early Xenopus embryonic cycles, the key replication timing factor Rif1 restrains the replication program globally, as absence of Rif1 leads to an accelerated temporal program and increased chromatin recruitment of key initiation factors.

Here the authors describe that the human origin recognition complex subunit 1 (ORC1) binds to RNAs transcribed from genes with origins of replication at their TSS impacting origin activation.

Here, using proteomics, molecular biology and sequencing, the authors demonstrate that OGT-dependent O-GlcNAcylation of H4S47 is important for replication-origin activation, presumably through regulating DDK-induced phosphorylation of the MCM complex.

A cardinal rule of DNA replication is to prevent any possibility of pre-replication complexes re-loading during S phase, risking genotoxic over-replication. But can this rule be broken in emergency situations to preserve genome integrity?

Replication stress fuels chromosomal instability, tumor heterogeneity and therapy resistance. The Sonic hedgehog pathway is now linked to an unorthodox form of replication stress in cerebellar granular-cell progenitors through deregulated firing of DNA replication origins, with implications for the pathogenesis, genomic instability and treatment of medulloblastoma.