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Cited by 15DNA Repair MechanismsPlant Molecular Biology ResearchPlant Genetic and Mutation Studies

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Identification of plants’ functional counterpart of the metazoan mediator of DNA Damage checkpoint 1

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Lorković, Zdravko J, Klingenbrunner, Michael, Cho, Chung Hyun, Berger, Frédéric·2024·EMBO Reports
DOI 10.1038/s44319-024-00107-8PMC PMC11014961

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Abstract

Induction of DNA damage triggers rapid phosphorylation of the histone H2A.X (γH2A.X). In animals, mediator of DNA damage checkpoint 1 (MDC1) binds γH2A.X through a tandem BRCA1 carboxyl-terminal (tBRCT) domain and mediates recruitment of downstream effectors of DNA damage response (DDR). However, readers of this modification in plants have remained elusive. We show that from the Arabidopsis BRCT domain proteome, BCP1-4 proteins with tBRCT domains are involved in DDR. Through its tBRCT domain BCP4 binds γH2A.X in vitro and localizes to DNA damage-induced foci in an H2A.X-dependent manner. BCP4 also contains a domain that interacts directly with NBS1 and thus acts as a functional counterpart of MDC1. We also show that BCP1, that contains two tBRCT domains, co-localizes with γH2A.X but it does not bind γH2A.X suggesting functional similarity with human PAXIP1. A phylogenetic analysis supports that PAXIP1 and MDC1 in metazoa and their plant counterparts evolved independently from common ancestors with tBRCT domains. Collectively, our study reveals missing components and provides mechanistic and evolutionary insights into plant DDR.

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  1. Akutsu N, Iijima K, Hinata T, Tauchi H (2007) Characterization of the plant homolog of Nijmegen breakage syndrome 1: Involvement in DNA repair and recombination. Biochem Biophys Res Commun 353:394–408 · DOI
  2. Almawi AW, Matthews LA, Guarne A (2017) FHA domains: phosphopeptide binding and beyond. Prog Biophys Mol Biol 127:105–110 · DOI
  3. Buchfink B, Xie C, Huson DH (2015) Fast and sensitive protein alignment using DIAMOND. Nat Methods 12:59–60 · DOI · Paper page
  4. Callebaut I, Mornon PJ (1997) From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett 400:25–30 · DOI
  5. Chapman JR, Jackson PS (2008) Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep 9:795–801 · DOI
  6. Cho CH, Park SI, Huang T-Y, Lee Y, Ciniglia C, Yadavalli HC, Yang SW, Bhattacharya D, Yoon HS (2023) Genome-wide signatures of adaptation to extreme environments in red algae. Nat Commun 14:10 · DOI · Paper page
  7. Ciccia A, Elledge JS (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40:179–204 · DOI · Paper page
  8. Coster G, Goldberg M (2010) The cellular response to DNA damage: a focus on MDC1 and its interacting proteins. Nucleus 1:166–178 · DOI
  9. Dronamraju R, Mason JM (2009) Recognition of double strand breaks by a mutator protein (MU2) in Drosophila melanogaster. PLoS Genet 5:e1000473 · DOI
  10. Escribano-Diaz C, Durocher D (2013) DNA repair pathway choice-a PTIP of the hat to 53BP1. EMBO Rep 14:665–666 · DOI
  11. Evans R, O’Neill M, Pritzel A, Antropova N, Senior A, Green T, Žídek A, Bates R, Blackwell S, Yim J et al (2022) Protein complex prediction with AlphaFold-Multimer. Preprint at https://doi.org/10.1101/2021.10.04.463034 · DOI · Paper page
  12. Fan T, Kang H, Wu D, Zhu X, Huang L, Wu J, Zhu Y (2022) Arabidopsis γ-H2A.X-INTERACTING PROTEIN participates in DNA damage response and safeguards chromatin stability. Nat Commun 13:7942 · DOI
  13. Ferrand J, Plessier A, Polo SE (2020) Control of the chromatin response to DNA damage: Histone proteins pull the strings. Semin Cell Dev Biol 113:75–87 · DOI
  14. Gatti M, Pinat S, Maiolica A, Rocchio F, Prato GM, Aebersold R, Penengo L (2015) RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Cell Rep 10:226–238 · DOI
  15. Gong Z, Cho Y-W, Kim J-E, Ge K, Chen J (2009) Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage. J Biol Chem 284:7284–7293 · DOI
  16. Hale CJ, Potok ME, Lopez J, Do T, Liu A, Gallego-Bartolome J, Michaels SD, Jacobsen SE (2016) Identification of multiple proteins coupling transcriptional gene silencing to genome stability in Arabidopsis thaliana. PLoS Genet 12:e1006092 · DOI
  17. Hari FJ, Spycher C, Jungmichel S, Pavic L, Stucki M (2010) A divalent FHA/BRCT-binding mechanism couples the MRE11-RAD50-NBS1 complex to damaged chromatin. EMBO Rep 11:387–392 · DOI
  18. Jowsey PA, Doherty AJ, Rouse J (2004) Human PTIP facilitates ATM-mediated activation of p53 and promotes cellular resistance to ionizing radiation. J Biol Chem 279:55562–55569 · DOI
  19. Kasravi A, Walter MF, Brand S, Mason JM, Biessmann H (1999) Molecular cloning and tissue-specific expression of the mutator2 Gene (mu2) in Drosophila melanogaster. Genetics 152:1025–1035 · DOI
  20. Katoh K, Standley DM (2013) MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30:772–780 · DOI · Paper page
  21. Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM et al (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318:1637–1640 · DOI
  22. Lafarge S, Montané MH (2003) Characterization of Arabidopsis thaliana ortholog of the human breast cancer susceptibility gene 1: AtBRCA1, strongly induced by gamma rays. Nucleic Acids Res 31:1148–1155 · DOI
  23. Lanz MC, Dibitetto D, Smolka MB (2019) DNA damage kinase signaling: checkpoint and repair at 30 years. EMBO J 38:e101801 · DOI
  24. Leebens-Mack et al (2019) One thousand plant transcriptomes and the phylogenomics of green plants. Nature 574:679–685 · DOI · Paper page
  25. Letunić I, Bork P (2021) Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49(W1):W293–W296 · DOI
  26. Leung CCY, Glover MJN (2011) BRCT domains: easy as one, two, three. Cell Cycle 10:2461–2470 · DOI
  27. Lloyd J, Chapman JR, Clapperton JA, Haire FL, Hartsuiker E, Li J, Carr AM, Jackson SP, Smerdon SJ (2009) A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage. Cell 139:100–111 · DOI · Paper page
  28. Lorković ZJ, Park C, Goiser M, Jiang D, Kurzbauer MT, Schlögelhofer P, Berger F (2017) Compartmentalization of DNA damage response between heterochromatin and euchromatin is mediated by distinct H2A histone variants. Curr Biol 27:1192–1199 · DOI
  29. Lou Z, Minter-Dykhouse K, Franco S, Gostissa M, Rivera MA, Celeste A, Manis JP, van Deursen J, Nussenzweig A, Paull TT et al (2006) MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol Cell 21:187–200 · DOI
  30. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131:887–900 · DOI
  31. Malik HS, Henikoff S (2003) Phylogenomics of the nucleosome. Nat Struct Biol 10:882–891 · DOI
  32. Manke IA, Lowery DM, Nguyen A, Yaffe MB (2003) BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302:636–639 · DOI · Paper page
  33. Mathilde G, Ghislaine G, Daniel V, Georges P (2003) The Arabidopsis MEI1 gene encodes a protein with five BRCT domains that is involved in meiosis-specific DNA repair events independent of SPO11-induced DSBs. Plant J 35:465–475 · DOI
  34. Melander F, Bekker-Jensen S, Falck J, Bartek J, Mailand N, Lukas J (2008) Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage-modified chromatin. J Cell Biol 181:213–226 · DOI
  35. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD, von Haeseler A, Lanfear R (2020) IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 37:1530–1534 · DOI · Paper page
  36. Mirman Z, de Lange T (2020) 53BP1: a DSB escort. Genes Dev 34:7–23 · DOI
  37. Muñoz IM, Jowsey PA, Toth R, Rouse J (2007) Phospho-epitope binding by the BRCT domains of hPTIP controls multiple aspects of the cellular response to DNA damage. Nucleic Acids Res 35:5312–5322 · DOI
  38. Nisa MU, Huang Y, Benhamed M, Raynaud C (2019) The plant DNA damage response: Signaling pathways leading to growth inhibition and putative role in response to stress conditions. Front Plant Sci 10:653 · DOI
  39. Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000) A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr Biol 10:886–895 · DOI · Paper page
  40. Qiu H, Price DC, Yang EC, Yoon HS, Bhattacharya D (2015) Evidence of ancient genome reduction in red algae (Rhodophyta). J Phycol 51:624–636 · DOI
  41. Reidt W, Wurz R, Wanieck K, Ch HH, Puchta H (2006) A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair in plants. EMBO J 25:4326–4337 · DOI
  42. Rogakou EP, Boon C, Redon C, Bonner WM (1999) Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol 146:905–916 · DOI · Paper page
  43. Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273:5858–5868 · DOI · Paper page
  44. Rosa M, Mittelsten Scheid O (2014) DNA damage sensitivity assays with Arabidopsis seedlings. Bio Protoc 4:e1093 · DOI
  45. Salguero I, Belotserkovskaya R, Coates J, Sczaniecka-Clift M, Demir M, Jhujh S, Wilson MD, Jackson SP (2019) MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance. Nat Commun 10:5191 · DOI
  46. Spycher C, Miller ES, Townsend K, Pavic L, Morrice NA, Janscak P, Stewart GS, Stucki M (2008) Constitutive phosphorylation of MDC1 physically links the MRE11-RAD50-NBS1 complex to damaged chromatin. J Cell Biol 181:227–240 · DOI
  47. Stucki M, Clapperton JA, Mohammad D, Yaffe MB, Smerdon SJ, Jackson SP (2005) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123:1213–1226 · DOI
  48. Turinetto V, Giachino C (2015) Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Nucleic Acids Res 43:2489–2498 · DOI
  49. Vladejić J, Yang F, Dvořák Tomaštíková E, Doležel J, Palecek JJ, Pecinka A (2022) Analysis of BRCT5 domain-containing proteins reveals a new component of DNA damage repair in Arabidopsis. Front Plant Sci 13:1023358 · DOI
  50. Wang X, Takenaka K, Takeda S (2010) PTIP promotes DNA double-strand break repair through homologous recombination. Genes Cells 15:243–254 · DOI
  51. Waterworth WM, Altun C, Armstrong SJ, Roberts N, Dean PJ, Young K, Weil FC, Bray MC, West EC (2007) NBS1 is involved in DNA repair and plays a synergistic role with ATM in mediating meiotic homologous recombination in plants. Plant J 52:41–52 · DOI
  52. Williams SR, Dodson EG, Limbo O, Yamada Y, Williams SJ, Guenther G, Classen S, Glover JNM, Iwasaki H, Russell P, Tainer AJ (2009) Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell 139:87–99 · DOI · Paper page
  53. Woods NT, Mesquita RD, Sweet M, Carvalho MA, Li X, Liu Y, Nguyen H, Thomas CE, Iversen Jr ES, Marsillac S et al (2012) Charting the landscape of tandem BRCT domain-mediated protein interactions. Sci Signal 5(242):rs6 · DOI
  54. Wu L, Luo K, Lou Z, Chen J (2008) MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks. Proc Natl Acad Sci USA 105:11200–11205 · DOI
  55. Xu Y, Xu D (2020) Repair pathway choice for double-strand breaks. Essays Biochem 64:765–777 · DOI
  56. Yelagandula R, Stroud H, Holec S, Zhou K, Feng S, Zhong X, Muthurajan UM, Nie X, Kawashima T, Groth M et al (2014) The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis. Cell 158:98–109 · DOI
  57. Yoshiyama K, Conklin PA, Huefner ND, Britt AB (2009) Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage. Proc Natl Acad Sci USA 106:12843–12848 · DOI
  58. Yoshiyama KO, Sakaguchi K, Kimura S (2013) DNA damage response in plants: conserved and variable response compared to animals. Biology 2:1338–1356 · DOI
  59. Yu C, Hou L, Huang Y, Cui X, Xu S, Wang L, Yan S (2023) The multi-BRCT domain protein DDRM2 promotes the recruitment of RAD51 to DNA damage sites to facilitate homologous recombination. New Phytol 238:1073–1084 · DOI
  60. Zhang J, Ma Z, Treszezamsky A, Powell SN (2005) MDC1 interacts with Rad51 and facilitates homologous recombination. Nat Struct Mol Biol 12:902–909 · DOI

Metadata

Authors
Lorković, Z. J., Klingenbrunner, M., Cho, C. H., & Berger, F.
Affiliations
Gregor Mendel Institute of Molecular Plant Biology (AT)
Corresponding author
  • Lorković, Zdravko J
  • Berger, Frédéric
ORCID
Venue
EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2024-03-04
Volume
25
Issue
4
Pages
1936-1961
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.1038/s44319-024-00107-8
PMC
PMC11014961
OpenAlex
W4392381579
Cited by
15
References
4
Citations by year
2026: 5 · 2025: 6 · 2024: 4
FWCI
2.04
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Austrian Science Fund (PAT 1104523)
  • National Research Foundation of Korea (RS-2023-00248097)
  • PlantS and ProTech facilitis at the Vienna BioCenter Core Facilities
  • BioOptics Facility and Molecular Biology Services from IMP/IMBA/GMI
  • Core funding from the Gregor Mendel Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Genetic and Mutation Studies
Keywords
MDC1, DNA damage response, γH2AX, histone H2A.X phosphorylation, BRCT domain, NBS1, Arabidopsis thaliana, DNA damage foci
MeSH terms
Animals, DNA Damage, DNA Repair, Humans, Nuclear Proteins, Phosphorylation, Phylogeny, Cell Cycle Proteins

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