MCM10 and SLD-2/RECQL4 jointly activate the CMG helicase during metazoan DNA replication initiation.

MCM10 and RECQL4 jointly activate the CMG helicase during metazoan DNA replication, with their absence causing lethal replication failure in vertebrate cells.

• Why it matters: Understanding how helicase activation is regulated in animal cells is crucial because defects in this process are linked to human diseases, yet the specific factors involved are not fully known.
• What they did: The study examined the roles of MCM10 and SLD-2/RECQL4 in C. elegans and mouse embryonic stem cells, revealing their recruitment to chromatin and partial redundancy in helicase activation, with gene deletions showing viability or lethality depending on context.
• The result: Findings demonstrate that metazoan helicase activation depends on two conserved factors, MCM10 and RECQL4, whose disruption impairs DNA replication and may contribute to disease mechanisms.