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TEBP-1 and TEBP-2 are double-stranded telomere binders required for fertility

ABSTRACT: Telomeres are the ends of linear chromosomes and consist of repetitive double- and single-stranded DNA sequences. Telomeres are bound by dedicated protein complexes, such as shelterin in mammals. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp 2 mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably, tebp 1;tebp-2 double mutant animals are synthetic sterile, with germlines showing signs of severe mitotic and meiotic arrest. These results define the first telomere-binding complex of C. elegans, including TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Caenorhabditis Elegans

SUBMITTER: F Butter

LAB HEAD: Falk Butter

PROVIDER: PXD019241 | Pride | 2021-03-09

REPOSITORIES: Pride

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ZNF524 directly binds telomeres and supports their integrity via TRF2/RAP1

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2023-10-21 | PXD024630 | Pride

ZNF524 directly binds telomeres and supports their integrity via TRF2/RAP1

2023-10-22 | PXD031416 | Pride

ZNF524 directly interacts with telomeric DNA and supports telomere integrity

Project description:Telomeres are nucleoprotein structures at the ends of linear chromosomes. In humans, they consist of TTAGGG repeats, which are bound by dedicated proteins such as the shelterin complex. This complex blocks unwanted DNA damage repair at telomeres, e.g. by suppressing non-homologous end joining (NHEJ) through its subunit TRF2. We here describe ZNF524, a zinc finger protein that directly binds telomeric repeats with nanomolar affinity and reveal the base-specific sequence recognition by co-crystallization with telomeric DNA. ZNF524 localizes to telomeres and specifically maintains the presence of the TRF2/RAP1 subcomplex at telomeres without affecting other shelterin members. Loss of ZNF524 concomitantly results in an increase in DNA damage signaling and recombination events. Overall, ZNF524 is a direct telomere-binding protein involved in the maintenance of telomere integrity.

2023-10-21 | PXD043084 | Pride

Chromatin modifiers and recombination factors promote a telomere fold-back structure, that is lost during replicative senescence

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2020-01-31 | PXD016772 | Pride

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