4bpx

From Proteopedia

(Difference between revisions)

Revision as of 03:42, 25 December 2014

Crystal structure of human primase in complex with the primase- binding motif of DNA polymerase alpha

Structural highlights

4bpx is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4bpu, 4bpw
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PRI1_HUMAN] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. [DPOLA_HUMAN] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.^[1]

Publication Abstract from PubMed

Initiation of DNA synthesis in genomic duplication depends on primase, the DNA-dependent RNA polymerase that synthesizes de novo the oligonucleotides that prime DNA replication. Due to the discontinuous nature of DNA replication, primase activity on the lagging strand is required throughout the replication process. In eukaryotic cells, the presence of primase at the replication fork is secured by its physical association with DNA polymerase alpha (Pol alpha), which extends the RNA primer with deoxynucleotides. Our knowledge of the mechanism that primes DNA synthesis is very limited, as structural information for the eukaryotic enzyme has proved difficult to obtain. Here, we describe the crystal structure of human primase in heterodimeric form consisting of full-length catalytic subunit and a C-terminally truncated large subunit. We exploit the crystallographic model to define the architecture of its nucleotide elongation site and to show that the small subunit integrates primer initiation and elongation within the same set of functional residues. Furthermore, we define in atomic detail the mode of association of primase to Pol alpha, the critical interaction that keeps primase tethered to the eukaryotic replisome.

Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering.,Kilkenny ML, Longo MA, Perera RL, Pellegrini L Proc Natl Acad Sci U S A. 2013 Sep 16. PMID:24043831^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Menissier-de Murcia J. Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication. Nucleic Acids Res. 1998 Apr 15;26(8):1891-8. PMID:9518481
↑ Kilkenny ML, Longo MA, Perera RL, Pellegrini L. Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering. Proc Natl Acad Sci U S A. 2013 Sep 16. PMID:24043831 doi:10.1073/pnas.1311185110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bpx"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4bpx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bpx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bpx RCSB], [http://www.ebi.ac.uk/pdbsum/4bpx PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/PRI1_HUMAN PRI1_HUMAN]] DNA primase is the polymerase that synthesizes small RNA primers for the Okazaki fragments made during discontinuous DNA replication. [[http://www.uniprot.org/uniprot/DPOLA_HUMAN DPOLA_HUMAN]] Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.<ref>PMID:9518481</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4bpx

From Proteopedia

Revision as of 03:42, 25 December 2014

Crystal structure of human primase in complex with the primase- binding motif of DNA polymerase alpha

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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