DNA replication in primary hepatocytes without the six-subunit ORC

• DOI: 10.7554/elife.102915.1
• Publication Date: 2024-12-31T17:25:06Z
• Authors: Róża K Przanowska; Yuechuan Chen; Takayuki-Okano Uc...; Etsuko Shibata; Xiaoxiao Hao; Isaac Segura Rueda; Kate Jensen; Piotr Przanowski; Anthony Trimboli; Yoshiyuki Shibata; Gustavo Leone; Anindya Dutta
• Keywords: Origin recognition complex; Licensing factor

The six subunit ORC is essential for initiation of DNA replication in eukaryotes. Cancer cell-lines culture can survive and replicate after genetic inactivation individual subunits, ORC1, ORC2 or ORC5. In primary cells, ORC1 was dispensable the mouse liver endo-reduplication, but this could be explained by homolog, CDC6, substituting to restore functional ORC. Here, we have created mice with a conditional deletion ORC2, which does not homolog. Although embryo fibroblasts require proliferation, hepatocytes synthesize cell endo-reduplicate vivo without ORC2. Mouse livers simultaneous both during normal development partial hepatectomy. Since endo-reduplication initiates synthesis like S phase these results unequivocally indicate that cancer lines, load MCM2-7 initiate