Origin replication complex

Newlon C. S. (1993) Two jobs for the origin replication complex. Science 262 1830. 

DNA replication proceeds in both directions from the replication origin (bidirectional), which means you need to form two sets of replication complexes. Each replication complex moves away from the origin (in opposite directions), unwinding and replicating both strands at each replication fork. 

The recent developments and ideas in the field of prebiotic chemistry can be combined with the concepts noted here to produce what we regard as a research outline, rather than a detailed hypothesis, directed toward a coherent theory of the origin of complex self-contained, self-replicating chiral assemblies. In what follows we present one possible scenario that is consistent with our current knowledge of chiral induction and amplification and with the nature of early Earth as well as early life. It is exciting that this fundamental question can be formulated in a way that allows systematic experimental testing as we enter the next century. 

HBOl Histone acetyltransferase bound to ORCl (origin-recognition complex subunit 1). A MYST family HAT involved in DNA replication. 

C. Keller, E.-M. Ladenburger, M. Kremer, and R. Knippers, The origin recognition complex marks a replication origin in the human TOPI gene promoter. J. Biol. Chem. 277,31430-31440 (2002). 

Control of origin activity occiu s via specific protein complexes that are boimd at certain times of the cell cycle to a replication origin. For replication initiation, two states of this protein complex are important, known as the pre-rephcation complex and the post-replication complex. 

The study of replication in yeast ARSs and artificial chromosomes has revealed that initiation of replication requires not only an initiator protein but a complex of six proteins that form an origin recognition complex (ORC).493 4953 This complex, which is essential to initiation of replication, may be joined by additional proteins in a prereplication complex. At least some of the ORC proteins have their homologous counterparts in metazoa, suggesting a highly conserved initiation machinery.4953-0... 

Hua XH, Newport J. Identification of a preinitiation step in DNA replication that is independent of origin recognition complex and cdc6, but dependent on cdk2. J Cell Biol 1998 140 271-281. Maiorano D, Lutzmann M, Mechali M. MCM proteins and DNA replication. Curr. Opin. Cell Biol. 2006 18 130-136. 

In anaphase and during Cl, a prereplication complex (pre-RC) is formed at replication initiation sites which contains the Cdc6 protein and the MCM proteins, in addition to the constitutively bound origin recognition complex (ORC). Formation of pre-RC is negatively regulated by the C2/M cyclin -CDK complex. The Cdc6 protein and the MDM proteins are removed at the Cl-S transition due to phosphorylation by the S-phase cyclin - CDK complex which allows the onset of DNA replication. The activity of the cyclin-CDK complexes is con-... 

Following activation of an origin and initiation of DNA synthesis, the Cdc6 protein becomes phosphorylated and dissociates from the origin, causing transition of the prereplication complex to a post-replication complex that is no longer able to initiate DNA replication. 

Unlike SV40 DNA, eukaryotic chromosomal DNA molecules contain multiple replication origins separated by tens to hundreds of kilobases. A sIx-subunIt protein called ORC, for origin recognition complex, binds to each origin and associates with other proteins required to load cellular hexameric helicases composed of six homologous MCM proteins. 

DNA replication Is Initiated from pre-replication complexes assembled at origins during early Gi. S-phase cyclln-CDK complexes simultaneously trigger Initiation from pre-replication complexes and Inhibit assembly of new pre-replication complexes by phosphorylating components of the pre-replication complex (see Figure 21-26). 

The study of replication in yeast ARSs and artificial chromosomes has revealed that initiation of replication requires not only an initiator protein but a complex of six proteins that form an origin recognition complex This complex, which is... 

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