Biochemistry, 4th Edition P92. Continuing Garrett and Grisham's innovative conceptual and organizing framework, "Essential Questions," BIOCHEMISTRY guides students through course concepts in a way that reveals the beauty and usefulness of biochemistry in the everyday world. Streamlined for increased clarity and readability, this edition also includes new photos and illustrations that show the subject matter consistently throughout the text. New end-of-chapter problems, MCAT practice questions, and the unparalleled text/media integration with the power of CengageNOW round out this exceptional package, giving you the tools you need to both master course concepts and develop critical problem-solving skills you can draw upon. | How Is DNA Replicated in Eukaryotic Cells 873 of proteins that interact with Dbp11 leads to the recruitment of DNA polymerase to the replication origins. The protein acronyms refer to DNA polymerase-binding Dpb and proteins encoded by genes that give a lethal phenotype when mutated in Dpb11 mutant strains of yeast Sld or synthetic-lethal with Dpb11 . Collectively these proteins are referred to as the 11-3-2 complex . The actions of S-CDK and Cdc7-Dbf4 trigger bidirectional DNA replication from each origin with the two diverging MCM complexes serving as helicases. Each helicase unwinds the duplex DNA to provide single-stranded templates for the DNA polymerases that follow. FIGURE The initiation of DNA replication in eukaryotic cells. Binding of the pre-RC to origins of replication is followed by loading of MCM hexameric helicases phosphorylation reactions mediated by S-CDK and Cdc7-Dbf4 and the binding of the 11-3-2 complex. The passage of the cell from G1 to S is defined by these events. DNA polymerases are recruited to the origins of replication where they can access single-stranded regions of DNA and initiate DNA synthesis. Proteins of the Prereplication Complex Are AAA ATPase Family Members Cdc6 the Orc proteins and MCM proteins are members of the AAA ATPase family a group of proteins characterized by sequence and structural homology ATPase activity and a general function as molecular chaperones. The binding of both ORC and Cdc6 to chromatin in the process of pre-RC assembly is ATP-depen-dent Figure . ORC with ATP bound can bind to origins of replication and recruit Cdc6 and Cdtl to form a pre-RC in which both ORC and Cdc6 have bound ATP. Cdc6 is required for the recruitment of the MCM proteins specifically a complex of MCM2-7 with ATP-dependent helicase activity. To establish the pre-RC MCM2-7 must be stably associated with the origin and this stability is achieved following ATP hydrolysis first by Cdc6 and then by ORC. Geminin Provides Another
