8D0B

Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template

Summary for 8D0B

• Entry DOI: 10.2210/pdb8d0b/pdb
• EMDB information: 27104
• Descriptor: CST complex subunit CTC1, CST complex subunit STN1, CST complex subunit TEN1, ... (8 entities in total)
• Functional Keywords: telomere, c-strand, complex, 4xtel-foldback dna template, replication-dna complex, replication/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 452791.30

Authors

He, Q.,Lin, X.,Chavez, B.L.,Agrawal, S.,Lusk, B.L.,Lim, C. (deposition date: 2022-05-26, release date: 2022-06-22, Last modification date: 2024-02-14)

Primary citation

He, Q.,Lin, X.,Chavez, B.L.,Agrawal, S.,Lusk, B.L.,Lim, C.J.
Structures of the human CST-Pol alpha-primase complex bound to telomere templates.
Nature, 608:826-832, 2022

PubMed Abstract: 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.

PubMed: 35830881
DOI: 10.1038/s41586-022-05040-1

Experimental method

ELECTRON MICROSCOPY (3.43 Å)