8d0b
From Proteopedia
(Difference between revisions)
| Line 10: | Line 10: | ||
== Function == | == Function == | ||
[[https://www.uniprot.org/uniprot/CTC1_HUMAN 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]<ref>PMID:19854130</ref> <ref>PMID:19854131</ref> <ref>PMID:22763445</ref> <ref>PMID:22863775</ref> <ref>PMID:25483097</ref> | [[https://www.uniprot.org/uniprot/CTC1_HUMAN 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]<ref>PMID:19854130</ref> <ref>PMID:19854131</ref> <ref>PMID:22763445</ref> <ref>PMID:22863775</ref> <ref>PMID:25483097</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The 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<ref>PMID:35830881</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8d0b" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 19:02, 7 September 2022
Human CST-DNA polymerase alpha/primase preinitiation complex bound to 4xTEL-foldback template
| |||||||||||
Categories: Homo sapiens | Large Structures | Agrawal S | Chavez BL | He Q | Lim C | Lin X | Lusk BL
