The TERB1 MYB domain suppresses telomere erosion in meiotic prophase I
Kexin Zhang,
Agata Tarczykowska,
Deepesh Kumar Gupta,
Devon F. Pendlebury,
Cassandra Zuckerman,
Jayakrishnan Nandakumar,
Hiroki Shibuya
Affiliations
Kexin Zhang
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-41390, Sweden
Agata Tarczykowska
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-41390, Sweden
Deepesh Kumar Gupta
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-41390, Sweden
Devon F. Pendlebury
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA
Cassandra Zuckerman
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
Jayakrishnan Nandakumar
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA
Hiroki Shibuya
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-41390, Sweden; Corresponding author
Summary: The meiosis-specific telomere-binding protein TERB1 anchors telomeres to the nuclear envelope and drives chromosome movements for the pairing of homologous chromosomes. TERB1 has an MYB-like DNA-binding (MYB) domain, which is a hallmark of telomeric DNA-binding proteins. Here, we demonstrate that the TERB1 MYB domain has lost its canonical DNA-binding activity. The analysis of Terb1 point mutant mice expressing TERB1 lacking its MYB domain showed that the MYB domain is dispensable for telomere localization of TERB1 and the downstream TERB2-MAJIN complex, the promotion of homologous pairing, and even fertility. Instead, the TERB1 MYB domain regulates the enrichment of cohesin and promotes the remodeling of axial elements in the early-to-late pachytene transition, which suppresses telomere erosion. Considering its conservation across metazoan phyla, the TERB1 MYB domain is likely to be important for the maintenance of telomeric DNA and thus for genomic integrity by suppressing meiotic telomere erosion over long evolutionary timescales.
