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TitleStructures of the human CST-Polα-primase complex bound to telomere templates.
Journal, issue, pagesNature, Vol. 608, Issue 7924, Page 826-832, Year 2022
Publish dateJul 13, 2022
AuthorsQixiang He / Xiuhua Lin / Bianca L Chavez / Sourav Agrawal / Benjamin L Lusk / Ci Ji Lim /
PubMed AbstractThe mammalian DNA polymerase-α-primase (Polα-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways such as lagging-strand ...The mammalian DNA polymerase-α-primase (Polα-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polα-primase, alone or in partnership with accessory proteins, performs its complicated multistep primer synthesis function is unknown. Here we show that CST, a single-stranded DNA-binding accessory protein complex for Polα-primase, physically organizes the enzyme for efficient primer synthesis. Cryogenic electron microscopy structures of the CST-Polα-primase preinitiation complex (PIC) bound to various types of telomere overhang reveal that template-bound CST partitions the DNA and RNA catalytic centres of Polα-primase into two separate domains and effectively arranges them in RNA-DNA synthesis order. The architecture of the PIC provides a single solution for the multiple structural requirements for the synthesis of RNA-DNA primers by Polα-primase. Several insights into the template-binding specificity of CST, template requirement for assembly of the CST-Polα-primase PIC and activation are also revealed in this study.
External linksNature / PubMed:35830881 / PubMed Central
MethodsEM (single particle)
Resolution3.43 - 4.27 Å
Structure data

EMDB-27097: Human CST-DNA polymerase alpha/primase preinitiation complex bound to 3xTEL template
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-27099: Human CST-DNA polymerase alpha/primase preinitiation complex bound to 3xTEL template - local refined domains and merged
Method: EM (single particle) / Resolution: 3.61 Å

EMDB-27104, PDB-8d0b:
Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template
Method: EM (single particle) / Resolution: 3.43 Å

EMDB-27107, PDB-8d0k:
Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template - PRIM2C advanced PIC
Method: EM (single particle) / Resolution: 4.27 Å

EMDB-27109: Human CST-DNA polymerase alpha/primase preinitiation complex bound to 6xTEL DNA template
Method: EM (single particle) / Resolution: 3.69 Å

Source
  • homo sapiens (human)
KeywordsREPLICATION/DNA / telomere / C-strand / complex / 4xTEL-foldback DNA template / REPLICATION-DNA complex / PRIM2C

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