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Abstract Duplex telomere binding proteins exhibit considerable structural and functional diversity in fungi. Herein we interrogate the activities and functions of two Myb-containing, duplex telomere repeat-binding factors inUstilago maydis, a basidiomycete that is evolutionarily distant from the standard fungi. These two telomere-binding proteins,UmTay1 andUmTrf2, despite having distinct domain structures, exhibit comparable affinities and sequence specificity for the canonical telomere repeats.UmTay1 specializes in promoting telomere replication and an ALT-like pathway, most likely by modulating the helicase activity of Blm.UmTrf2, in contrast, is critical for telomere protection; transcriptional repression ofUmtrf2leads to severe growth defects and profound telomere aberrations. Comparative analysis ofUmTay1 homologs in different phyla reveals broad functional diversity for this protein family and provides a case study for how DNA-binding proteins can acquire and lose functions at various chromosomal locations. Our findings also point to stimulatory effect of telomere protein on ALT inUstilago maydisthat may be conserved in other systems.
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This content will become publicly available on December 9, 2025
Ustilago maydis Trf2 ensures genome stability by antagonizing Blm-mediated telomere recombination: Fine-tuning DNA repair factor activity at telomeres through opposing regulations
TRF2 is an essential and conserved double-strand telomere binding protein that stabilizes chromosome ends by suppressing DNA damage response and aberrant DNA repair. Herein we investigated the mechanisms and functions of the Trf2 ortholog in the basidiomycete fungusUstilago maydis, which manifests strong resemblances to metazoans with regards to the telomere and DNA repair machinery. We showed thatUmTrf2 binds to Blmin vitroand inhibits Blm-mediated unwinding of telomeric DNA substrates. Consistent with a similar inhibitory activityin vivo, over-expression of Trf2 induces telomere shortening, just like deletion ofblm, which is required for efficient telomere replication. While the loss of Trf2 engenders growth arrest and multiple telomere aberrations, these defects are fully suppressed by the concurrent deletion ofblmormre11(but not other DNA repair factors). Over-expression of Blm alone triggers aberrant telomere recombination and the accumulation of aberrant telomere structures, which are blocked by concurrent Trf2 over-expression. Together, these findings highlight the suppression of Blm as a key protective mechanism of Trf2. Notably,U.maydisharbors another double-strand telomere-binding protein (Tay1), which promotes Blm activity to ensure efficient replication. We found that deletion oftay1partially suppresses the telomere aberration of Trf2-depleted cells. Our results thus point to opposing regulation of Blm helicase by telomere proteins as a strategy for optimizing both telomere maintenance and protection. We also show that aberrant transcription of both telomere G- and C-strand is a recurrent phenotype of telomere mutants, underscoring another potential similarity between double strand breaks and de-protected telomeres.
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- Award ID(s):
- 2246561
- PAR ID:
- 10577908
- Editor(s):
- Zappulla, David C
- Publisher / Repository:
- PLOS
- Date Published:
- Journal Name:
- PLOS Genetics
- Volume:
- 20
- Issue:
- 12
- ISSN:
- 1553-7404
- Page Range / eLocation ID:
- e1011515
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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