{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T23:16:06Z","timestamp":1776726966041,"version":"3.51.2"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2018-T2-1-100"],"award-info":[{"award-number":["MOE2018-T2-1-100"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011744","name":"National University Health System","doi-asserted-by":"publisher","award":["NUHSRO\/2013\/127\/STB\/B2B-06"],"award-info":[{"award-number":["NUHSRO\/2013\/127\/STB\/B2B-06"]}],"id":[{"id":"10.13039\/501100011744","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolic pathway, and its loss of function through polymorphisms is often associated with human conditions, including cancer, congenital heart disease, and Down syndrome. MTHFR is also required in the maintenance of heterochromatin, a crucial determinant of genomic stability and precise chromosomal segregation. Here, we characterize the function of a fission yeast gene met11+, which encodes a protein that is highly homologous to the mammalian MTHFR. We show that, although met11+ is not essential for viability, its disruption increases chromosome missegregation and destabilizes constitutive heterochromatic regions at pericentromeric, sub-telomeric and ribosomal DNA (rDNA) loci. Transcriptional silencing at these sites were disrupted, which is accompanied by the reduction in enrichment of histone H3 lysine 9 dimethylation (H3K9me2) and binding of the heterochromatin protein 1 (HP1)-like Swi6. The met11 null mutant also dominantly disrupts meiotic fidelity, as displayed by reduced sporulation efficiency and defects in proper partitioning of the genetic material during meiosis. Interestingly, the faithful execution of these meiotic processes is synergistically ensured by cooperation among Met11, Rec8, a meiosis-specific cohesin protein, and the shugoshin protein Sgo1, which protects Rec8 from untimely cleavage. Overall, our results suggest a key role for Met11 in maintaining pericentromeric heterochromatin for precise genetic inheritance during mitosis and meiosis.<\/jats:p>","DOI":"10.3390\/ijms22020639","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T11:36:11Z","timestamp":1610364971000},"page":"639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Fission Yeast Methylenetetrahydrofolate Reductase Ensures Mitotic and Meiotic Chromosome Segregation Fidelity"],"prefix":"10.3390","volume":"22","author":[{"given":"Kim Kiat","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hwei Yee","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan Yee","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi Bing","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulysses Tsz Fung","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahesh","family":"Choolani","sequence":"additional","affiliation":[{"name":"National University Health System (NUHS), Singapore 119228, Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-2131","authenticated-orcid":false,"given":"Ee Sin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"},{"name":"National University Health System (NUHS), Singapore 119228, Singapore"},{"name":"NUS Graduate School of Integrative Sciences &amp; Engineering, National University of Singapore, Singapore 117456, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/nrm3382","article-title":"New insights into nucleosome and chromatin structure: An ordered state or a disordered affair?","volume":"13","author":"Luger","year":"2012","journal-title":"Nat. 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