| Structural highlights
Function
[HRR25_YEAST] Associated with repair of damaged DNA and meiosis. Phosphorylates serine and threonine. Can use casein as a substrate. [MAM1_YEAST] Component of the monopolin complex which promotes monoorientation during meiosis I, required for chromosome segregation during meiosis.[1] [2] [3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
In budding yeast, the monopolin complex mediates sister kinetochore cross-linking and co-orientation in meiosis I. The CK1delta kinase Hrr25 is critical for sister kinetochore co-orientation, but its roles are not well understood. Here, we present the structures of Hrr25 and its complex with the monopolin subunit Mam1. Hrr25 possesses a "central domain" that packs tightly against the kinase C-lobe, adjacent to the binding site for Mam1. Together, the Hrr25 central domain and Mam1 form a novel, contiguous embellishment to the Hrr25 kinase domain that affects Hrr25 conformational dynamics and enzyme kinetics. Mam1 binds a hydrophobic surface on the Hrr25 N-lobe that is conserved in CK1delta-family kinases, suggesting a role for this surface in recruitment and/or regulation of these enzymes throughout eukaryotes. Finally, using purified proteins, we find that Hrr25 phosphorylates the kinetochore receptor for monopolin, Dsn1. Together with our new structural insights into the fully assembled monopolin complex, this finding suggests that tightly localized Hrr25 activity modulates monopolin complex-kinetochore interactions through phosphorylation of both kinetochore and monopolin complex components.
Structure of the Saccharomyces cerevisiae Hrr25:Mam1 monopolin subcomplex reveals a novel kinase regulator.,Ye Q, Ur SN, Su TY, Corbett KD EMBO J. 2016 Oct 4;35(19):2139-2151. Epub 2016 Aug 4. PMID:27491543[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Toth A, Rabitsch KP, Galova M, Schleiffer A, Buonomo SB, Nasmyth K. Functional genomics identifies monopolin: a kinetochore protein required for segregation of homologs during meiosis i. Cell. 2000 Dec 22;103(7):1155-68. PMID:11163190
- ↑ Rabitsch KP, Toth A, Galova M, Schleiffer A, Schaffner G, Aigner E, Rupp C, Penkner AM, Moreno-Borchart AC, Primig M, Esposito RE, Klein F, Knop M, Nasmyth K. A screen for genes required for meiosis and spore formation based on whole-genome expression. Curr Biol. 2001 Jul 10;11(13):1001-9. PMID:11470404
- ↑ Rabitsch KP, Petronczki M, Javerzat JP, Genier S, Chwalla B, Schleiffer A, Tanaka TU, Nasmyth K. Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I. Dev Cell. 2003 Apr;4(4):535-48. PMID:12689592
- ↑ Enyenihi AH, Saunders WS. Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics. 2003 Jan;163(1):47-54. PMID:12586695
- ↑ Clyne RK, Katis VL, Jessop L, Benjamin KR, Herskowitz I, Lichten M, Nasmyth K. Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I. Nat Cell Biol. 2003 May;5(5):480-5. PMID:12717442 doi:http://dx.doi.org/10.1038/ncb977
- ↑ Lee BH, Amon A. Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation. Science. 2003 Apr 18;300(5618):482-6. Epub 2003 Mar 27. PMID:12663816 doi:http://dx.doi.org/10.1126/science.1081846
- ↑ Katis VL, Matos J, Mori S, Shirahige K, Zachariae W, Nasmyth K. Spo13 facilitates monopolin recruitment to kinetochores and regulates maintenance of centromeric cohesion during yeast meiosis. Curr Biol. 2004 Dec 29;14(24):2183-96. PMID:15620645 doi:http://dx.doi.org/S096098220400956X
- ↑ Petronczki M, Chwalla B, Siomos MF, Yokobayashi S, Helmhart W, Deutschbauer AM, Davis RW, Watanabe Y, Nasmyth K. Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II. J Cell Sci. 2004 Jul 15;117(Pt 16):3547-59. Epub 2004 Jun 29. PMID:15226378 doi:http://dx.doi.org/10.1242/jcs.01231
- ↑ Ye Q, Ur SN, Su TY, Corbett KD. Structure of the Saccharomyces cerevisiae Hrr25:Mam1 monopolin subcomplex reveals a novel kinase regulator. EMBO J. 2016 Oct 4;35(19):2139-2151. Epub 2016 Aug 4. PMID:27491543 doi:http://dx.doi.org/10.15252/embj.201694082
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