| Title | Endoreduplication of the mouse genome in the absence of ORC1. |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Okano-Uchida T, Kent LN, Ouseph MM, McCarty B, Frank JJ, Kladney R, Cuitiño MC, Thompson JC, Coppola V, Asano M, Leone G |
| Journal | Genes Dev |
| Volume | 32 |
| Issue | 13-14 |
| Pagination | 978-990 |
| Date Published | 2018 07 01 |
| ISSN | 1549-5477 |
| Keywords | Adenosine Triphosphatases, Animals, Cell Division, Cell Proliferation, Embryonic Development, Endoreduplication, Enzyme Activation, Female, Gene Deletion, Genome, Hepatocytes, Liver Regeneration, Mice, Mitosis, Origin Recognition Complex, Placenta, Pregnancy |
| Abstract | The largest subunit of the origin recognition complex (ORC1) is essential for assembly of the prereplicative complex, firing of DNA replication origins, and faithful duplication of the genome. Here, we generated knock-in mice with sites flanking exons encoding the critical ATPase domain of ORC1. Global or tissue-specific ablation of ORC1 function in mouse embryo fibroblasts and fetal and adult diploid tissues blocked DNA replication, cell lineage expansion, and organ development. Remarkably, ablation in extraembryonic trophoblasts and hepatocytes, two polyploid cell types in mice, failed to impede genome endoreduplication and organ development and function. Thus, ORC1 in mice is essential for mitotic cell divisions but dispensable for endoreduplication. We propose that DNA replication of mammalian polyploid genomes uses a distinct ORC1-independent mechanism. |
| DOI | 10.1101/gad.311910.118 |
| Alternate Journal | Genes Dev |
| PubMed ID | 29967292 |
| PubMed Central ID | PMC6075035 |
| Grant List | P30 CA016058 / CA / NCI NIH HHS / United States R01 CA121275 / CA / NCI NIH HHS / United States |
Related Faculty:
Madhu Ouseph, M.D., Ph.D.