This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
8d0k
From Proteopedia
Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template - PRIM2C advanced PIC
Structural highlights
Disease[CTC1_HUMAN] Coats plus syndrome;Dyskeratosis congenita. The disease is caused by mutations affecting the gene represented in this entry. Function[CTC1_HUMAN] Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).[UniProtKB:Q5SUQ9][1] [2] [3] [4] [5] Publication Abstract from PubMedThe mammalian DNA polymerase-alpha-primase (Polalpha-primase) complex is essential for DNA metabolism, providing the de novo RNA-DNA primer for several DNA replication pathways(1-4) such as lagging-strand synthesis and telomere C-strand fill-in. The physical mechanism underlying how Polalpha-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 Polalpha-primase, physically organizes the enzyme for efficient primer synthesis. Cryogenic electron microscopy structures of the CST-Polalpha-primase preinitiation complex (PIC) bound to various types of telomere overhang reveal that template-bound CST partitions the DNA and RNA catalytic centres of Polalpha-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 Polalpha-primase. Several insights into the template-binding specificity of CST, template requirement for assembly of the CST-Polalpha-primase PIC and activation are also revealed in this study. Structures of the human CST-Polalpha-primase complex bound to telomere templates.,He Q, Lin X, Chavez BL, Agrawal S, Lusk BL, Lim CJ Nature. 2022 Aug;608(7924):826-832. doi: 10.1038/s41586-022-05040-1. Epub 2022, Jul 13. PMID:35830881[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
Categories: Homo sapiens | Large Structures | Agrawal S | Chavez BL | He Q | Lim C | Lin X | Lusk BL
