title: Geminin a multi task protein involved in cancer pathophysiology and developmental process: A review.
abstract: DNA replicates in a timely manner with each cell division. Multiple proteins and factors are involved in the initiation of DNA replication including a dynamic interaction between Cdc10-dependent transcript (Cdt1) and Geminin (GMNN). A conformational change between GMNN-Cdt1 heterotrimer and heterohexamer complex is responsible for licensing or inhibition of the DNA replication. This molecular switch ensures a faithful DNA replication during each S phase of cell cycle. GMNN inhibits Cdt1-mediated minichromosome maintenance helicases (MCM) loading onto the chromatin-bound origin recognition complex (ORC) which results in the inhibition of pre-replication complex assembly. GMNN modulates DNA replication by direct binding to Cdt1, and thereby alters its stability and activity. GMNN is involved in various stages of development such as pre-implantation, germ layer formation, cell commitment and specification, maintenance of genome integrity at mid blastula transition, epithelial to mesenchymal transition during gastrulation, neural development, organogenesis and axis patterning. GMNN interacts with different proteins resulting in enhanced hematopoietic stem cell activity thereby activating the development-associated genes' transcription. GMNN expression is also associated with cancer pathophysiology and development. In this review we discussed the structure and function of GMNN in detail. Inhibitors of GMNN and their role in DNA replication, repair, cell cycle and apoptosis are reviewed. Further, we also discussed the role of GMNN in virus infected host cells.
authors.affiliation: School of Basic and Applied Sciences, Centre for Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, 151001, India.
authors.forename: Prem Prakash
authors.initials: PP
authors.lastname: Kushwaha
authors.affiliation: School of Basic and Applied Sciences, Centre for Animal Sciences, Central University of Punjab, Bathinda, 151001, India.
authors.forename: Krishna Chaitanya
authors.initials: KC
authors.lastname: Rapalli
authors.affiliation: School of Basic and Applied Sciences, Centre for Biochemistry and Microbial Sciences, Central University of Punjab, Bathinda, 151001, India. Electronic address: shashankbiochemau@gmail.com.
authors.forename: Shashank
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism*; D064248:Geminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011487:Protein Conformation
chemical_list: D064248:Geminin
keywords: Cancer; Cell cycle; DNA replication; Development; Geminin; Inhibitors