Site-to-site mutational dissection of fission yeast cohesin reveals its dynamics.

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Tác giả: Saidaiguli Abulimiti, Jie Wang, Li Wang, Qi Wei, Xingya Xu, Yichen Zhang

Ngôn ngữ: eng

Ký hiệu phân loại: 306.8747 Marriage and family

Thông tin xuất bản: England : G3 (Bethesda, Md.) , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 747449

Cohesin is a heteropentameric protein complex that holds sister chromatids together from S phase to anaphase. Its two structural maintenance of chromosomes (SMC) subunits form a heterodimer, consisting of an ATPase head domain and a hinge domain connected by long coiled coils. Kleisin subunit associates with the head. Here, using Schizosaccharomyces pombe, we genetically dissected cohesin dynamics based on the relationship between the mutations causing temperature-sensitive and their suppressor mutations. First, we identified suppressor mutations that could rescue the lethality caused by cohesin ATPase mutations. Mutations in the DNA binding domain of cohesin loader Mis4, or in cell-cycle genes encoding MBF transcription factor complex or Wee1 kinase, rescued both Psm1 and Psm3 ATPase mutants. Then, we performed targeted mutagenesis in both ATPase domains for single-amino-acid substitutions, that can rescue the lethality of a kleisin ts mutant at restrictive temperature. Comparison of mutations obtained in Psm1 and Psm3 ATPase domains revealed that analogous mutations in the two ATPase domains were frequently observed. Last, suppressors of a coiled-coil mutation were mapped in coiled coils, indicating that proper folding of coiled coils is critical for cohesin functions. Suppressors of a hinge interface mutation frequently located at the other hinge interface, indicating that the two cohesin hinge interfaces work collaboratively in hinge-hinge interactions. Overall, genetic dissection of the relationship between cohesin lethal mutations and their suppressor mutations reflects cohesin dynamics in vivo.
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