An Inactive Geminin Mutant That Binds Cdt1

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An Inactive Geminin Mutant That Binds Cdt1

The initiation of DNA replication is tightly regulated in order to ensure that the genome duplicates only once per cell cycle. In vertebrate cells, the unstable regulatory protein Geminin prevents a second round of DNA replication by inhibiting the essential replication factor Cdt1. Cdt1 recruits mini-chromosome maintenance complex (MCM2-7), the replication helicase, into the pre-replication co...

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A human replication initiation protein, Cdt1, is a central player in the cell cycle regulation of DNA replication, and geminin down-regulates Cdt1 function by direct binding. It has been demonstrated that Cdt1 hyperfunction resulting from Cdt1-geminin imbalance, for example, by geminin silencing with small interfering RNA, induces DNA re-replication and eventual cell death in some cancer-derive...

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3. A role for Cdt1 and Geminin in regulating genomic integrity and cancer promotion in tumor cells 4. Geminin and Cdt1 as markers for cancer prognosis 5. Perspectives: Geminin and Cdt1 as players in the molecular mechanisms of carcinogenesis

Cdt1 and its inhibitor Geminin are important regulators of replication licensing. In normal cells, a critical balance between these two proteins ensures that firing of each origin along the genome will take place only once per cell cycle. Cdt1 overexpression in cell lines and animals leads to aberrant replication, activates DNA damage checkpoints and predisposes for malignant transformation. Ge...

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ژورنال

عنوان ژورنال: Genes

سال: 2015

ISSN: 2073-4425

DOI: 10.3390/genes6020252