A tool to control excess replication
Replication origin flexibility mitigates the hazards of inaccurate and untimely genome duplication by assembling prereplication complexes in excess.
Cells maintain distinct molecular signaling pathways to sustain replication origin dormancy.
Chromatin states, transcription, and 3D genome architecture dictate initiation frequency and replication timing in a cell type-specific manner.
Misregulated replication increases the frequency of breaks in fragile sites and facilitates the formation of extrachromosomal DNA, which, in turn, increases replication stress through over- and under-replication.
The same pathways that protect normal cells from over-replication become liabilities in cancer, and precision oncology can weaponize them to selectively induce replication catastrophe.
https://www.cell.com/trends/genetics/fulltext/S0168-9525(26)00057-0
