POT-3 preferentially binds the terminal DNA-repeat on the telomeric G-overhang
Date
25/01/2023Metadata
Show full item recordAbstract
Eukaryotic chromosomes typically end in 3′ telomeric overhangs. The safeguarding of telomeric single-stranded DNA overhangs is carried out by factors related to the protection of telomeres 1 (POT1) protein in humans. Of the three POT1-like proteins in Caenorhabditis elegans, POT-3 was the only member thought to not play a role at telomeres. Here, we provide evidence that POT-3 is a bona fide telomere-binding protein. Using a new loss-of-function mutant, we show that the absence of POT-3 causes telomere lengthening and increased levels of telomeric C-circles. We find that POT-3 directly binds the telomeric G-strand in vitro and map its minimal DNA binding site to the six-nucleotide motif, GCTTAG. We further show that the closely related POT-2 protein binds the same motif, but that POT-3 shows higher sequence selectivity. Crucially, in contrast to POT-2, POT-3 prefers binding sites immediately adjacent to the 3′ end of DNA. These differences are significant as genetic analyses reveal that pot-2 and pot-3 do not function redundantly with each other in vivo. Our work highlights the rapid evolution and specialisation of telomere binding proteins and places POT-3 in a unique position to influence activities that control telomere length.
Citation
Yu , X , Gray , S & Ferreira , H 2023 , ' POT-3 preferentially binds the terminal DNA-repeat on the telomeric G-overhang ' , Nucleic Acids Research , vol. 51 , no. 2 , pp. 610–618 . https://doi.org/10.1093/nar/gkac1203
Publication
Nucleic Acids Research
Status
Peer reviewed
ISSN
0305-1048Type
Journal article
Rights
Copyright © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Description
Funding: The China Scholarship Scheme supported Xupeng Yu [201904910787]; some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs [P40 OD010440]. Funding for open access charge: Scottish Higher Education Digital Library Consortium (SHEDL) Read and Publish agreement.Collections
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