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Title

3D architecture of DNA Pol alpha reveals the functional core of multi-subunit replicative polymerases

AuthorsKlinge, Sebastian; Ñez-Ramírez, Rafael; Llorca, Óscar ; Pellegrini, Luca
KeywordsDNA polymerase α
DNA replication
electron microscopy
X-ray crystallography
Issue Date8-Jul-2009
PublisherNature Publishing Group
CitationEMBO Journal 28(13):1978-1987(2009)
AbstractEukaryotic DNA replication requires the coordinated activity of the multi-subunit DNA polymerases: Pol α, Pol δ and Pol ε. The conserved catalytic and regulatory B subunits associate in a constitutive heterodimer that represents the functional core of all three replicative polymerases. Here, we combine X-ray crystallography and electron microscopy (EM) to describe subunit interaction and 3D architecture of heterodimeric yeast Pol α. The crystal structure of the C-terminal domain (CTD) of the catalytic subunit bound to the B subunit illustrates a conserved mechanism of accessory factor recruitment by replicative polymerases. The EM reconstructions of Pol α reveal a bilobal shape with separate catalytic and regulatory modules. Docking of the B–CTD complex in the EM reconstruction shows that the B subunit is tethered to the polymerase domain through a structured but flexible linker. Our combined findings provide a structural template for the common functional architecture of the three major replicative DNA polymerases
Description10 páginas, 7 figuras -- PAGS nros. 1978-1987
Publisher version (URL)http://dx.doi.org/10.1038/emboj.2009.150
URIhttp://hdl.handle.net/10261/55775
DOI10.1038/emboj.2009.150
ISSN0261-4189
E-ISSN1460-2075
Appears in Collections:(CIB) Artículos
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