Hachiman is a genome integrity sensor.
| العنوان: | Hachiman is a genome integrity sensor. |
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| المؤلفون: | Tuck OT; Department of Chemistry, University of California, Berkeley, Berkeley, CA USA.; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA., Adler BA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA USA., Armbruster EG; School of Biological Sciences, University of California San Diego, La Jolla, CA USA., Lahiri A; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Hu JJ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Zhou J; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Pogliano J; School of Biological Sciences, University of California San Diego, La Jolla, CA USA., Doudna JA; Department of Chemistry, University of California, Berkeley, Berkeley, CA USA.; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA USA.; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA USA.; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA USA.; Gladstone Institutes, University of California, San Francisco, San Francisco, CA USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 29. Date of Electronic Publication: 2024 Feb 29. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Hachiman is a broad-spectrum antiphage defense system of unknown function. We show here that Hachiman comprises a heterodimeric nuclease-helicase complex, HamAB. HamA, previously a protein of unknown function, is the effector nuclease. HamB is the sensor helicase. HamB constrains HamA activity during surveillance of intact dsDNA. When the HamAB complex detects DNA damage, HamB helicase activity liberates HamA, unleashing nuclease activity. Hachiman activation degrades all DNA in the cell, creating 'phantom' cells devoid of both phage and host DNA. We demonstrate Hachiman activation in the absence of phage by treatment with DNA-damaging agents, suggesting that Hachiman responds to aberrant DNA states. Phylogenetic similarities between the Hachiman helicase and eukaryotic enzymes suggest this bacterial immune system has been repurposed for diverse functions across all domains of life. Competing Interests: Competing interest statement J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Mammoth Biosciences and Scribe Therapeutics, and a director of Altos, Johnson & Johnson and Tempus. J.A.D. is a scientific advisor to Caribou Biosciences, Intellia Therapeutics, Mammoth Biosciences, Inari, Scribe Therapeutics, Felix Biosciences and Algen. J.A.D. also serves as Chief Science Advisor to Sixth Street and a Scientific Advisory Board member at The Column Group. J.A.D. conducts academic research projects sponsored by Roche and Apple Tree Partners. J.P. has an equity interest in Linnaeus Bioscience Incorporated and receives income. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. |
| References: | Nat Methods. 2019 Nov;16(11):1153-1160. (PMID: 31591578) Mol Syst Biol. 2011 Oct 11;7:539. (PMID: 21988835) Annu Rev Immunol. 2018 Apr 26;36:667-694. (PMID: 29677479) Nucleic Acids Res. 2018 Jan 4;46(D1):D708-D717. (PMID: 29040670) Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530. (PMID: 29872003) EMBO J. 1998 Nov 16;17(22):6437-48. (PMID: 9822590) Curr Opin Struct Biol. 2010 Jun;20(3):313-24. (PMID: 20456941) RNA Biol. 2013 Jan;10(1):4-18. (PMID: 22922795) Cell. 2023 Apr 27;186(9):1863-1876.e16. (PMID: 37030292) Nat Rev Immunol. 2008 Jul;8(7):559-68. (PMID: 18575461) Annu Rev Genet. 1998;32:379-413. (PMID: 9928485) J Biol Chem. 2008 Feb 22;283(8):5118-26. (PMID: 18056710) Genes Genet Syst. 2014;89(2):51-60. (PMID: 25224971) Cold Spring Harb Perspect Biol. 2014 Oct 23;6(11):a016550. (PMID: 25341919) Nat Biotechnol. 2017 Nov;35(11):1026-1028. (PMID: 29035372) Science. 2020 Aug 28;369(6507):1077-1084. (PMID: 32855333) Nat Methods. 2017 Mar;14(3):290-296. (PMID: 28165473) Mol Cell. 2018 Oct 18;72(2):355-368.e4. (PMID: 30270105) Proc Natl Acad Sci U S A. 1978 Oct;75(10):4838-42. (PMID: 368801) Nat Methods. 2022 Jun;19(6):679-682. (PMID: 35637307) Nat Struct Mol Biol. 2010 Sep;17(9):1152-3. (PMID: 20802486) Sci Rep. 2020 Nov 10;10(1):19422. (PMID: 33173044) BMC Struct Biol. 2007 Jun 20;7:40. (PMID: 17584917) Nucleic Acids Res. 2021 Nov 8;49(19):10868-10878. (PMID: 34606606) Annu Rev Biophys. 2008;37:317-36. (PMID: 18573084) Annu Rev Virol. 2020 Sep 29;7(1):371-384. (PMID: 32559405) Nucleic Acids Res. 2023 Aug 25;51(15):8115-8132. (PMID: 37395408) Science. 2013 Apr 19;340(6130):353-6. (PMID: 23599494) Nat Rev Genet. 2008 Mar;9(3):204-17. (PMID: 18227811) Nat Struct Mol Biol. 2009 Jun;16(6):667-9. (PMID: 19448616) Science. 2018 Mar 2;359(6379):. (PMID: 29371424) Microbiol Mol Biol Rev. 2006 Dec;70(4):876-87. (PMID: 17158702) Proteins. 1997 May;28(1):41-52. (PMID: 9144789) Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):531-544. (PMID: 29872004) Mol Cell. 2022 Dec 1;82(23):4471-4486.e9. (PMID: 36395770) Elife. 2021 Mar 19;10:. (PMID: 33739282) Proc Natl Acad Sci U S A. 1985 Jan;82(2):307-11. (PMID: 2982149) Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844) J Mol Biol. 1968 Dec;38(3):395-411. (PMID: 4305016) Commun Biol. 2021 Jul 15;4(1):874. (PMID: 34267316) Nucleic Acids Res. 2021 Jul 2;49(W1):W293-W296. (PMID: 33885785) Nucleic Acids Res. 2008 Dec;36(22):7029-42. (PMID: 18986999) Science. 2017 Feb 24;355(6327):. (PMID: 28209641) Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1373-8. (PMID: 24379377) Nat Rev Mol Cell Biol. 2011 Apr;12(4):235-45. (PMID: 21427765) Cell. 2004 Apr 2;117(1):1-3. (PMID: 15066275) J Struct Biol. 2021 Jun;213(2):107702. (PMID: 33582281) Bacteriophage. 2011 Jan;1(1):46-49. (PMID: 21687534) Bioinformatics. 2012 Jun 15;28(12):1647-9. (PMID: 22543367) Cell Host Microbe. 2023 Mar 8;31(3):343-355.e5. (PMID: 36893733) mSphere. 2023 Dec 20;8(6):e0037223. (PMID: 37882551) Bioinformatics. 2020 Aug 1;36(15):4350-4352. (PMID: 32637988) Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002) Nat Commun. 2023 May 11;14(1):2725. (PMID: 37169801) Nature. 2020 Jan;577(7789):244-248. (PMID: 31819262) Virol J. 2010 Dec 03;7:358. (PMID: 21129203) Science. 2017 Jan 13;355(6321):194-197. (PMID: 28082593) Curr Opin Struct Biol. 2014 Feb;24:106-14. (PMID: 24480304) Nat Struct Mol Biol. 2007 Jul;14(7):647-52. (PMID: 17558417) J Biol Chem. 2011 May 6;286(18):15832-40. (PMID: 21398521) Mol Biol Evol. 2018 Feb 1;35(2):518-522. (PMID: 29077904) Mol Biol Evol. 2015 Jan;32(1):268-74. (PMID: 25371430) Cell. 2020 Jul 9;182(1):38-49.e17. (PMID: 32544385) Nature. 1997 Aug 28;388(6645):903-6. (PMID: 9278055) Annu Rev Biochem. 2014;83:697-725. (PMID: 24635478) J Bacteriol. 1979 Nov;140(2):424-35. (PMID: 227840) RNA. 2018 Feb;24(2):127-142. (PMID: 29093021) Nat Methods. 2020 Dec;17(12):1214-1221. (PMID: 33257830) Nucleic Acids Res. 2023 May 22;51(9):4467-4487. (PMID: 36987874) PLoS Pathog. 2021 Dec 9;17(12):e1010072. (PMID: 34882751) Mol Microbiol. 1999 Feb;31(4):1149-59. (PMID: 10096082) Nucleic Acids Res. 2005 Jun 30;33(11):3678-90. (PMID: 15994460) Cell Host Microbe. 2022 Apr 13;30(4):570-582.e7. (PMID: 35421352) Annu Rev Biochem. 2007;76:23-50. (PMID: 17506634) Annu Rev Microbiol. 2003;57:301-22. (PMID: 14527281) Mol Cell. 2023 Nov 16;83(22):4093-4105.e7. (PMID: 37879335) Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45. (PMID: 26553804) RNA Biol. 2013 Jan;10(1):33-43. (PMID: 22995828) Bacteriophage. 2015 Aug 25;5(4):e1086500. (PMID: 26904381) Nat Methods. 2009 May;6(5):343-5. (PMID: 19363495) Nucleic Acids Res. 2006;34(15):4206-15. (PMID: 16935882) Nat Commun. 2022 May 10;13(1):2561. (PMID: 35538097) Nucleic Acids Res. 2004 Mar 19;32(5):1792-7. (PMID: 15034147) Protein Sci. 2018 Jan;27(1):14-25. (PMID: 28710774) Annu Rev Biochem. 1991;60:477-511. (PMID: 1883202) |
| معلومات مُعتمدة: | R01 GM129245 United States GM NIGMS NIH HHS; T32 GM133351 United States GM NIGMS NIH HHS; U01 AI142817 United States AI NIAID NIH HHS; U19 AI135990 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20240311 Latest Revision: 20240319 |
| رمز التحديث: | 20240319 |
| مُعرف محوري في PubMed: | PMC10925250 |
| DOI: | 10.1101/2024.02.29.582594 |
| PMID: | 38464307 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2024.02.29.582594 |
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