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Review
. 2018 Dec:53:131-139.
doi: 10.1016/j.sbi.2018.08.003. Epub 2018 Sep 12.

A structural view of the initiators for chromosome replication

Kin Fan On  1 , Matt Jaremko  1 , Bruce Stillman  2 , Leemor Joshua-Tor  3
Affiliations
Review

A structural view of the initiators for chromosome replication

Kin Fan On et al. Curr Opin Struct Biol. 2018 Dec.
No abstract available

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Figures

Fig. 1
Fig. 1
Models for origin recognition and helicase loading in the three domains of life and in viruses. In eukaryotes, bacteria and archaea, the origin is first recognized by the origin recognition machinery, with concomitant DNA remodeling occurring in bacteria and archaea. The replicative helicase is then recruited and directly interacts with the origin recognition complex. ATP binding but not hydrolysis is required for this interaction (see text). In eukaryotes, multiple origin recognition proteins may be required for loading a double hexameric form of the helicase. After helicase loading, ATP hydrolysis allows for reiterate assembly of helicases on other locations on the DNA. In viruses (human papillomavirus is shown as an example in this case), the viral helicase often serves the function of both origin recognition and self-assembly onto DNA into the mature helicase. In papillomavirus, a double-trimeric assembly of the helicase complex, linked to origin melting, is a prerequisite for the fully functional helicase complexes to be formed in subsequent steps in an ATP hydrolysis-dependent manner (for simplicity, other auxiliary factors are omitted in the diagram).
Fig. 2
Fig. 2
Overall structures of ORC from different species. (a) Schematic alignment of ORC subunits and CDC6. The RecA (or RecA-like) and Lid domains are part of the AAA+ domain common in this clade of AAA+ ATPases. A winged helix (WH) domain is at the C-terminus in all subunits except for ORC6. Structures of (b, e) Saccharomyces cerevisiae ORC, (c, f) Drosophila melanogaster ORC and (d, g and h) human ORC shown in perpendicular views.
Fig. 3
Fig. 3
Comparison of the ORC4 subunit from S. cerevisiae, D. melanogaster, and H. sapiens. ScOrc4 contains an α-helix insertion located in the major groove of DNA. This α-helix is missing in human and Drosophila ORC4.
Fig. 4
Fig. 4
Comparison of loaders of ring-shaped proteins from bacteriophage T4 and S. cerevisiae. (a) Schematic of the T4 DNA polymerase clamp loader (gp44 and gp62) bound to the gp45 clamp [an analogue of the eukaryotic PCNA]. (b) Surface representation of the structure of the T4 clamp loader bound to the clamp. (c) Cartoon representation of gp44 subunits A,B,C bound to primer-template DNA (red and blue strands) (d) Schematic of the S. cerevisiae helicase loader (ScORC+Cdc6) and pre-helicase complex (MCM+Cdt1). (e) Surface representation of the structure of ScOrc-Cdc6 bound to the MCM complex and Cdt1 on double strand origin DNA (f) Cartoon representation of ScORC subunits 1,4,5 bound to double-stranded DNA [red and blue strands]. (c) and (f) illustrate the corkscrew orientation of the subunits in the clamp loader and in ORC, both of which surround dsDNA.
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References

    1. Leonard AC, Mechali M: DNA replication origins. Cold Spring Harb Perspect Biol 2013, 5:a010116. - PMC - PubMed
    1. Abbas T, Keaton MA, Dutta A: Genomic instability in cancer. Cold Spring Harb Perspect Biol 2013, 5:a012914. - PMC - PubMed
    1. Klingseisen A, Jackson AP: Mechanisms and pathways of growth failure in primordial dwarfism. Genes Dev 2011, 25:2011–2024. - PMC - PubMed
    1. Siddiqui K, On KF, Diffley JF: Regulating DNA replication in eukarya. Cold Spring Harb Perspect Biol 2013, 5. - PMC - PubMed
    1. Jacob F, Brenner S: [On the regulation of DNA synthesis in bacteria: the hypothesis of the replicon]. C R Hebd Seances Acad Sci 1963, 256:298–300. - PubMed

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