Molecular basis for the initiation of DNA primer synthesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F22%3A00127814" target="_blank" >RIV/00216224:14310/22:00127814 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41586-022-04695-0" target="_blank" >https://www.nature.com/articles/s41586-022-04695-0</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41586-022-04695-0" target="_blank" >10.1038/s41586-022-04695-0</a>
Alternative languages
Result language
angličtina
Original language name
Molecular basis for the initiation of DNA primer synthesis
Original language description
During the initiation of DNA replication, oligonucleotide primers are synthesized de novo by primases and are subsequently extended by replicative polymerases to complete genome duplication. The primase-polymerase (Prim-Pol) superfamily is a diverse grouping of primases, which includes replicative primases and CRISPR-associated primase-polymerases (CAPPs) involved in adaptive immunity(1-3). Although much is known about the activities of these enzymes, the precise mechanism used by primases to initiate primer synthesis has not been elucidated. Here we identify the molecular bases for the initiation of primer synthesis by CAPP and show that this mechanism is also conserved in replicative primases. The crystal structure of a primer initiation complex reveals how the incoming nucleotides are positioned within the active site, adjacent to metal cofactors and paired to the templating single-stranded DNA strand, before synthesis of the first phosphodiester bond. Furthermore, the structure of a Prim-Pol complex with double-stranded DNA shows how the enzyme subsequently extends primers in a processive polymerase mode. The structural and mechanistic studies presented here establish how Prim-Pol proteins instigate primer synthesis, revealing the requisite molecular determinants for primer synthesis within the catalytic domain. This work also establishes that the catalytic domain of Prim-Pol enzymes, including replicative primases, is sufficient to catalyse primer formation.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature
ISSN
0028-0836
e-ISSN
1476-4687
Volume of the periodical
605
Issue of the periodical within the volume
7911
Country of publishing house
DE - GERMANY
Number of pages
7
Pages from-to
767-773
UT code for WoS article
000790783300002
EID of the result in the Scopus database
2-s2.0-85129589357