ArticlePLoS genetics2011
Misregulation of Scm3p/HJURP causes chromosome instability in Saccharomyces cerevisiae and human cells.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Centromere and kinetochore gene misexpression predicts cancer patient survival and response to radiotherapy and chemotherapy.Nature communications · 2016Pooled it
- Keeping it centered: decoding the activities that regulate yeast histone H3 variant Cse4 and confine it to centromeres.Frontiers in cell and developmental biology · 2026Review
- Evidence of centromeric histone 3 chaperone involved in DNA damage repair pathway in budding yeast.eLife · 2025Article
- HJURP modulates cell proliferation and chemoresistance via the MYC/TOP2A transcriptional axis in gastric cancer.Frontiers in molecular biosciences · 2025Article
- Mck1-mediated proteolysis of CENP-A prevents mislocalization of CENP-A for chromosomal stability in Saccharomyces cerevisiae.Genetics · 2024Article
- HJURP is recruited to double-strand break sites and facilitates DNA repair by promoting chromatin reorganization.Oncogene · 2024Article
- The cysteine-rich domain in CENP-A chaperone Scm3HJURP ensures centromere targeting and kinetochore integrity.Nucleic acids research · 2024Article
- Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.Molecular biology of the cell · 2023Article
- Advances in holliday junction recognition protein (HJURP): Structure, molecular functions, and roles in cancer.Frontiers in cell and developmental biology · 2023Review
- Prognostic value of Holliday junction-recognizing protein and its correlation with immune infiltrates in lung adenocarcinoma.Oncology letters · 2022Article
- Cdc48Ufd1/Npl4 segregase removes mislocalized centromeric histone H3 variant CENP-A from non-centromeric chromatin.Nucleic acids research · 2022Article
- HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer.International journal of biological sciences · 2022Article
- Cdc7-mediated phosphorylation of Cse4 regulates high-fidelity chromosome segregation in budding yeast.Molecular biology of the cell · 2021Article
- Reduced gene dosage of histone H4 prevents CENP-A mislocalization and chromosomal instability in Saccharomyces cerevisiae.Genetics · 2021Article
- Gene networks and transcriptional regulators associated with liver cancer development and progression.BMC medical genomics · 2021Article
- R-loops at centromeric chromatin contribute to defects in kinetochore integrity and chromosomal instability in budding yeast.Molecular biology of the cell · 2021Article
- Dbf4-Dependent Kinase (DDK)-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A inG3 (Bethesda, Md.) · 2020Article
- HJURP knockdown disrupts clonogenic capacity and increases radiation-induced cell death of glioblastoma cells.Cancer gene therapy · 2020Article
- Skp, Cullin, F-box (SCF)-Met30 and SCF-Cdc4-Mediated Proteolysis of CENP-A Prevents Mislocalization of CENP-A for Chromosomal Stability in Budding Yeast.PLoS genetics · 2020Article
- Upregulation of Holliday junction recognition protein predicts poor prognosis and biochemical recurrence in patients with prostate cancer.Oncology letters · 2019Article
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
The kinetochore (centromeric DNA and associated proteins) is a key determinant for high fidelity chromosome transmission. Evolutionarily conserved Scm3p is an essential component of centromeric chromatin and is required for assembly and function of kinetochores in humans, fission yeast, and budding yeast. Overexpression of HJURP, the mammalian homolog of budding yeast Scm3p, has been observed in lung and breast cancers and is associated with poor prognosis; however, the physiological relevance of these observations is not well understood. We overexpressed SCM3 and HJURP in Saccharomyces cerevisiae and HJURP in human cells and defined domains within Scm3p that mediate its chromosome loss phenotype. Our results showed that the overexpression of SCM3 (GALSCM3) or HJURP (GALHJURP) caused chromosome loss in a wild-type yeast strain, and overexpression of HJURP led to mitotic defects in human cells. GALSCM3 resulted in reduced viability in kinetochore mutants, premature separation of sister chromatids, and reduction in Cse4p and histone H4 at centromeres. Overexpression of CSE4 or histone H4 suppressed chromosome loss and restored levels of Cse4p at centromeres in GALSCM3 strains. Using mutant alleles of scm3, we identified a domain in the N-terminus of Scm3p that mediates its interaction with CEN DNA and determined that the chromosome loss phenotype of GALSCM3 is due to centromeric association of Scm3p devoid of Cse4p/H4. Furthermore, we determined that similar to other systems the centromeric association of Scm3p is cell cycle regulated. Our results show that altered stoichiometry of Scm3p/HJURP, Cse4p, and histone H4 lead to defects in chromosome segregation. We conclude that stringent regulation of HJURP and SCM3 expression are critical for genome stability.
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Registered trials
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