The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I

Zhang, Kexin; Tarczykowska, Agata; Gupta, Deepesh Kumar; Pendlebury, Devon F.; Zuckerman, Cassandra; Nandakumar, Jayakrishnan; Shibuya, Hiroki

doi:10.1016/j.celrep.2021.110289

Cited by 6 publications

(1 citation statement)

References 45 publications

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“…A few cases of protein–protein interactions involving plant and human Myb domains have been previously documented ( Grotewold et al 2000 ; Ying et al 2000 ; Zimmermann et al 2004 ). The Myb domain of a meiosis-specific telomeric protein, TERB1, also has a function that is independent of its binding to DNA, presumably involving an interaction with SA3 ( Shibuya et al 2014 ; Zhang et al 2017 , 2022 ). There are two more Myb domains in shelterin: one in TRF2, which directly binds to telomeric DNA, and another one in Rap1, which has a basic surface and does not bind DNA ( Hanaoka et al 2001 ).…”

Section: Discussionmentioning

confidence: 99%

TRF1 uses a noncanonical function of TFIIH to promote telomere replication

2022

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Telomeric DNA challenges the replisome and requires TRF1 for efficient duplication. TRF1 recruits the BLM helicase, but BLM loss does not explain the extensive telomere fragility, ATR signaling, and sister telomere associations (STAs) induced by TRF1 deletion. Here, we document that Helix2 of the TRFH domain and Helix1 of the Myb domain of TRF1 are required for efficient telomere replication. Mutation of both helices generated a TRF1 separation-of-function mutant (TRF1-E83K/LW-TI) that induced severe telomere replication defects but no ATR signaling or STAs. We identified the transcription and nucleotide excision repair (NER) factor TFIIH as a critical effector of TRF1. Loss of TFIIH subunits, but no other NER factors, caused the same telomere replication phenotypes as the TRF1-E83K/LW-TI mutant independent of the effects on TRF1 expression. TFIIH subunits coimmunoprecipitated with wild-type TRF1 but not with TRF1-E83K/LW-TI. These results establish that the major mechanism by which TRF1 ensures telomere replication involves a noncanonical function of TFIIH.

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Section: Discussionmentioning

confidence: 99%

TRF1 uses a noncanonical function of TFIIH to promote telomere replication

2022

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Comprehensive analyses of 435 goat transcriptomes provides insight into male reproduction

Xu,

Zhang,

Duan

et al. 2024

International Journal of Biological Macromolecules

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Caenorhabditis elegans telomere-binding proteins TEBP-1 and TEBP-2 adapt the Myb module to dimerize and bind telomeric DNA

Padmanaban,

Lambacher,

Tesmer

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Protecting chromosome ends from misrecognition as double-stranded (ds) DNA breaks is fundamental to eukaryotic viability. The protein complex shelterin prevents a DNA damage response at mammalian telomeres. Mammalian shelterin proteins TRF1 and TRF2 and their homologs in yeast and protozoa protect telomeric dsDNA. N-terminal homodimerization and C-terminal Myb-domain-mediated dsDNA binding are two structural hallmarks of end protection by TRF homologs. Yet our understanding of how Caenorhabditis elegans protects its telomeric dsDNA is limited. Recently identified C. elegans proteins TEBP-1 (also called DTN-1) and TEBP-2 (also called DTN-2) are functional homologs of TRF proteins, but how they bind DNA and whether or how they dimerize is not known. TEBP-1 and TEBP-2 harbor three Myb-containing domains (MCDs) and no obvious dimerization domain. We demonstrate biochemically that only the third MCD binds DNA. We solve the X-ray crystal structure of TEBP-2 MCD3 with telomeric dsDNA to reveal the structural mechanism of telomeric dsDNA protection in C. elegans . Mutagenesis of the DNA-binding site of TEBP-1 and TEBP-2 compromises DNA binding in vitro, and increases DNA damage signaling, lengthens telomeres, and decreases brood size in vivo. Via an X-ray crystal structure, biochemical validation of the dimerization interface, and SEC-MALS analysis, we demonstrate that MCD1 and MCD2 form a composite dimerization module that facilitates not only TEBP-1 and TEBP-2 homodimerization but also heterodimerization. These findings provide fundamental insights into C. elegans telomeric dsDNA protection and highlight how different eukaryotes have evolved distinct strategies to solve the chromosome end protection problem.

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The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I

Cited by 6 publications

References 45 publications

TRF1 uses a noncanonical function of TFIIH to promote telomere replication

TRF1 uses a noncanonical function of TFIIH to promote telomere replication

Comprehensive analyses of 435 goat transcriptomes provides insight into male reproduction

Caenorhabditis elegans telomere-binding proteins TEBP-1 and TEBP-2 adapt the Myb module to dimerize and bind telomeric DNA

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