دورية أكاديمية
An acidic loop in the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates.
العنوان: | An acidic loop in the FHA domain of the yeast meiosis-specific kinase Mek1 interacts with a specific motif in a subset of Mek1 substrates. |
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المؤلفون: | Weng Q; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA., Wan L; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA., Straker GC; Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada., Deegan TD; MRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, UK DD1 5EH, UK.; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK., Duncker BP; Department of Biology, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada., Neiman AM; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA., Luk E; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA., Hollingsworth NM; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794-5215, USA. |
المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 May 25. Date of Electronic Publication: 2024 May 25. |
نوع المنشور: | Journal Article; Preprint |
اللغة: | English |
بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
مستخلص: | The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at the double strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80, regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a five amino acid sequence, RPSKR, located between the DNA binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a non-canonical interaction with this motif. A second protein, the 5'-3' helicase Rrm3, similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in the MEK1 acidic loop validated the AlphaFold model, in that they specifically disrupt two-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint, and in certain circumstances exhibit more severe phenotypes compared to the NDT80 mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif. |
التعليقات: | Update in: Genetics. 2024 Jul 09:iyae106. doi: 10.1093/genetics/iyae106. (PMID: 38979911) |
References: | Mol Cell Biol. 2007 Aug;27(15):5456-67. (PMID: 17526735) Cell. 1990 May 4;61(3):419-36. (PMID: 2185891) Cell Mol Life Sci. 2010 Jun;67(12):1957-70. (PMID: 20148280) Nucleic Acids Res. 1992 Feb 11;20(3):449-57. (PMID: 1741279) Genes Dev. 1997 Jan 1;11(1):106-18. (PMID: 9000054) Dev Cell. 2008 Sep;15(3):401-415. (PMID: 18691940) Cell. 2001 Jul 13;106(1):59-70. (PMID: 11461702) PLoS One. 2016 May 23;11(5):e0155931. (PMID: 27214570) Cell Rep. 2015 Oct 6;13(1):80-92. (PMID: 26411679) J Biol Chem. 1999 Jan 15;274(3):1783-90. (PMID: 9880561) Science. 2003 Apr 18;300(5618):482-6. (PMID: 12663816) Nature. 2010 Apr 8;464(7290):937-41. (PMID: 20348905) EMBO J. 2017 Sep 1;36(17):2488-2509. (PMID: 28694245) PLoS Biol. 2016 Feb 12;14(2):e1002369. (PMID: 26870961) Genetics. 1992 Oct;132(2):387-402. (PMID: 1427035) Methods Mol Biol. 2011;745:135-49. (PMID: 21660693) Genetics. 2017 May;206(1):497-512. (PMID: 28249986) Sci Signal. 2010 Feb 16;3(109):ra12. (PMID: 20159853) Mol Cell. 2008 Aug 8;31(3):324-36. (PMID: 18691965) Mol Cell. 2012 Apr 13;46(1):43-53. (PMID: 22500736) J Am Chem Soc. 2005 Apr 20;127(15):5288-9. (PMID: 15826144) Mol Cell. 2000 Nov;6(5):1169-82. (PMID: 11106755) Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30577-30588. (PMID: 33199619) Mol Cell. 2019 Apr 18;74(2):231-244.e9. (PMID: 30850330) Mol Gen Genet. 1989 Aug;218(2):293-301. (PMID: 2550770) Chromosoma. 2019 Sep;128(3):249-265. (PMID: 31069484) Curr Genet. 2019 Jun;65(3):631-641. (PMID: 30671596) Genetics. 2001 Dec;159(4):1511-25. (PMID: 11779793) Mol Cell. 1999 Sep;4(3):387-94. (PMID: 10518219) Mol Cell. 1998 Apr;1(5):685-96. (PMID: 9660952) Cell. 2001 Jul 13;106(1):47-57. (PMID: 11461701) Genetics. 2011 Oct;189(2):423-39. (PMID: 21840861) Yeast. 1998 Jul;14(10):953-61. (PMID: 9717241) Mol Biol Cell. 2004 Jan;15(1):11-23. (PMID: 14595109) Mol Cell. 2003 Dec;12(6):1525-36. (PMID: 14690605) Microbiol Mol Biol Rev. 2012 Mar;76(1):1-15. (PMID: 22390969) Nature. 2008 Jul 24;454(7203):479-85. (PMID: 18615017) Cell. 2012 Oct 26;151(3):603-18. (PMID: 23101628) PLoS Biol. 2007 Nov 6;5(11):e299. (PMID: 17988174) Cell. 2012 Apr 13;149(2):334-47. (PMID: 22500800) Genes Dev. 2006 Jul 1;20(13):1766-75. (PMID: 16818607) Biochem Soc Trans. 2017 Oct 15;45(5):1159-1171. (PMID: 28900015) Cell. 2011 Mar 4;144(5):719-31. (PMID: 21376234) Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16087-92. (PMID: 12441400) PLoS Genet. 2011 Nov;7(11):e1002351. (PMID: 22072981) Cell. 2010 Dec 10;143(6):924-37. (PMID: 21145459) Mol Cell Biol. 1995 Dec;15(12):6572-81. (PMID: 8524222) Curr Biol. 2010 Oct 12;20(19):1707-16. (PMID: 20888230) Mol Cell Biol. 1995 Jul;15(7):3813-22. (PMID: 7791788) Nature. 2005 Aug 18;436(7053):1053-7. (PMID: 16107854) Nucleic Acids Res. 2006;34(15):4147-53. (PMID: 16935874) Nat Methods. 2007 Jun;4(6):511-6. (PMID: 17486086) Mol Biol Cell. 2005 Dec;16(12):5804-18. (PMID: 16221890) Prog Biophys Mol Biol. 2017 Aug;127:105-110. (PMID: 27939759) Nature. 1996 Oct 31;383(6603):840-3. (PMID: 8893012) J Biol Chem. 2002 Nov 22;277(47):45331-7. (PMID: 12239216) Annu Rev Genet. 2014;48:187-214. (PMID: 25421598) PLoS Genet. 2014 Jan;10(1):e1004005. (PMID: 24465215) Chromosoma. 2019 Sep;128(3):181-198. (PMID: 31236671) Genes Dev. 2008 Mar 15;22(6):786-95. (PMID: 18347097) Cell. 1997 Feb 7;88(3):375-84. (PMID: 9039264) Genetics. 2024 Jul 15;:. (PMID: 39005070) Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844) Genetics. 2017 Dec;207(4):1313-1333. (PMID: 28986445) Cell. 1995 Dec 1;83(5):783-91. (PMID: 8521495) Science. 1998 Oct 23;282(5389):699-705. (PMID: 9784122) Genes (Basel). 2020 Feb 20;11(2):. (PMID: 32093266) Cell. 1993 Nov 19;75(4):791-803. (PMID: 8242750) Cell. 2004 Apr 2;117(1):29-45. (PMID: 15066280) Nucleic Acids Res. 2021 May 7;49(8):4522-4533. (PMID: 33823531) PLoS Biol. 2015 Dec 18;13(12):e1002329. (PMID: 26682552) Nucleic Acids Res. 2012 Dec;40(22):11416-27. (PMID: 23047948) Genome Res. 2004 Jun;14(6):1188-90. (PMID: 15173120) Sci Rep. 2020 Feb 25;10(1):3379. (PMID: 32099015) Mol Cell. 2009 Nov 13;36(3):393-404. (PMID: 19917248) Genes Dev. 1993 Apr;7(4):555-69. (PMID: 8384581) Mol Cell Biol. 2000 Sep;20(18):6646-58. (PMID: 10958662) J Cell Biol. 1997 Mar 10;136(5):957-67. (PMID: 9060462) Genes Dev. 1995 Jul 15;9(14):1728-39. (PMID: 7622037) PLoS Genet. 2013;9(12):e1003978. (PMID: 24367271) PLoS Genet. 2018 Nov 29;14(11):e1007832. (PMID: 30496175) Nat Rev Genet. 2001 Apr;2(4):280-91. (PMID: 11283700) FEBS Lett. 2002 Feb 20;513(1):58-66. (PMID: 11911881) Methods Enzymol. 2018;601:275-307. (PMID: 29523236) Mol Cell. 2008 Aug 8;31(3):313-23. (PMID: 18691964) Eukaryot Cell. 2004 Jun;3(3):598-609. (PMID: 15189982) Cold Spring Harb Perspect Biol. 2014 Dec 04;7(1):a016659. (PMID: 25475089) Genes Dev. 2008 Oct 1;22(19):2627-32. (PMID: 18832066) Nucleic Acids Res. 2024 Feb 28;52(4):1753-1762. (PMID: 38117984) Genetics. 1997 Jul;146(3):781-95. (PMID: 9215887) Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R203-8. (PMID: 17911163) Cell. 2008 Mar 7;132(5):758-70. (PMID: 18329363) Genetics. 1989 May;122(1):19-27. (PMID: 2659436) Genes Dev. 2002 Jun 1;16(11):1383-96. (PMID: 12050116) Yeast. 1999 Oct;15(14):1541-53. (PMID: 10514571) J Biol Chem. 2014 Jan 31;289(5):2589-99. (PMID: 24285546) Trends Biochem Sci. 2018 May;43(5):380-394. (PMID: 29544874) PLoS Genet. 2016 Aug 02;12(8):e1006226. (PMID: 27483004) Genes Dev. 2020 Dec 1;34(23-24):1605-1618. (PMID: 33184224) PLoS Genet. 2022 Dec 12;18(12):e1010407. (PMID: 36508468) Genetics. 1997 Jul;146(3):797-816. (PMID: 9215888) Genetics. 2010 Jul;185(3):771-82. (PMID: 20421598) Proc Natl Acad Sci U S A. 1988 Aug;85(16):6057-61. (PMID: 3413075) Genetics. 2004 Nov;168(3):1205-18. (PMID: 15579680) J Biol Chem. 2010 Dec 31;285(53):41244-54. (PMID: 21036905) Genes Dev. 1991 Dec;5(12B):2392-404. (PMID: 1752435) |
معلومات مُعتمدة: | R01 GM072540 United States GM NIGMS NIH HHS; R01 GM147795 United States GM NIGMS NIH HHS; R35 GM140684 United States GM NIGMS NIH HHS |
فهرسة مساهمة: | Keywords: FHA domain; Mek1; Rrm3; meiosis; recombination |
تواريخ الأحداث: | Date Created: 20240603 Latest Revision: 20240722 |
رمز التحديث: | 20240722 |
مُعرف محوري في PubMed: | PMC11142242 |
DOI: | 10.1101/2024.05.24.595751 |
PMID: | 38826409 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2692-8205 |
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DOI: | 10.1101/2024.05.24.595751 |