Reference: Deshpande I, et al. (2019) The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. EMBO J 38(20):e101744

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Abstract


In Saccharomyces cerevisiae, the silent information regulator (SIR) proteins Sir2/3/4 form a complex that suppresses transcription in subtelomeric regions and at the homothallic mating-type (HM) loci. Here, we identify a non-canonical BRCA1 C-terminal domain (H-BRCT) in SIR4, which is responsible for tethering telomeres to the nuclear periphery. We show that SIR4 H-BRCT and the closely related DBF4 H-BRCT serve as selective phospho-epitope recognition domains that bind to a variety of phosphorylated target peptides. We present detailed structural information about the binding mode of established SIR4 interactors (ESC1, Ty5, UBP10) and identify several novel interactors of SIR4 H-BRCT, including the E3 ubiquitin ligase TOM1. Based on these findings, we propose a phospho-peptide consensus motif for interaction with SIR4 H-BRCT and DBF4 H-BRCT. Ablation of the SIR4 H-BRCT phospho-peptide interaction disrupts SIR-mediated repression and perinuclear localization. In conclusion, the SIR4 H-BRCT domain serves as a hub for recruitment of phosphorylated target proteins to heterochromatin to properly regulate silencing and nuclear order.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H
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