The dual role of the RETINOBLASTOMA-RELATED protein in the DNA damage response is coordinated by the interaction with LXCXE-containing proteins.
DNA damage response (DDR)
LXCXE motif
NAC044
RETINOBLASTOMA-RELATED PROTEIN (RBR)
programmed cell death (PCD)
Journal
The Plant journal : for cell and molecular biology
ISSN: 1365-313X
Titre abrégé: Plant J
Pays: England
ID NLM: 9207397
Informations de publication
Date de publication:
06 Feb 2024
06 Feb 2024
Historique:
revised:
10
01
2024
received:
08
02
2022
accepted:
18
01
2024
medline:
7
2
2024
pubmed:
7
2
2024
entrez:
6
2
2024
Statut:
aheadofprint
Résumé
Living organisms possess mechanisms to safeguard genome integrity. To avoid spreading mutations, DNA lesions are detected and cell division is temporarily arrested to allow repair mechanisms. Afterward, cells either resume division or respond to unsuccessful repair by undergoing programmed cell death (PCD). How the success rate of DNA repair connects to later cell fate decisions remains incompletely known, particularly in plants. The Arabidopsis thaliana RETINOBLASTOMA-RELATED1 (RBR) protein and its partner E2FA, play both structural and transcriptional functions in the DNA damage response (DDR). Here we provide evidence that distinct RBR protein interactions with LXCXE motif-containing proteins guide these processes. Using the N849F substitution in the RBR B-pocket domain, which specifically disrupts binding to the LXCXE motif, we show that these interactions are dispensable in unchallenging conditions. However, N849F substitution abolishes RBR nuclear foci and promotes PCD and growth arrest upon genotoxic stress. NAC044, which promotes growth arrest and PCD, accumulates after the initial recruitment of RBR to foci and can bind non-focalized RBR through the LXCXE motif in a phosphorylation-independent manner, allowing interaction at different cell cycle phases. Disrupting NAC044-RBR interaction impairs PCD, but their genetic interaction points to opposite independent roles in the regulation of PCD. The LXCXE-binding dependency of the roles of RBR in the DDR suggests a coordinating mechanism to translate DNA repair success to cell survival. We propose that RBR and NAC044 act in two distinct DDR pathways, but interact to integrate input from both DDR pathways to decide upon an irreversible cell fate decision.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 32070874
Organisme : Consejo Nacional de Ciencia y Tecnología
ID : 383871
Informations de copyright
© 2024 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.
Références
Berckmans, B. & De Veylder, L. (2009) Transcriptional control of the cell cycle. Current Opinion in Plant Biology, 12, 599-605.
Biedermann, S., Harashima, H., Chen, P., Heese, M., Bouyer, D., Sofroni, K. et al. (2017) The retinoblastoma homolog RBR1 mediates localization of the repair protein RAD51 to DNA lesions in Arabidopsis. The EMBO Journal, 36, 1279-1297.
Boniotti, M.B. & Gutierrez, C. (2001) A cell-cycle-regulated kinase activity phosphorylates plant retinoblastoma protein and contains, in Arabidopsis, a CDKA/cyclin D complex. The Plant Journal, 28, 341-350.
Bourbousse, C., Vegesna, N. & Law, J.A. (2018) SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America, 115, E12453-E12462.
Bourgo, R.J., Thangavel, C., Ertel, A., Bergseid, J., Kathleen McClendon, A., Wilkens, L. et al. (2011) RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent mechanism of transcriptional control. Molecular Cell, 43, 663-672.
Bouyer, D., Heese, M., Chen, P., Harashima, H., Roudier, F., Gruttner, C. et al. (2018) Genome-wide identification of RETINOBLASTOMA RELATED 1 binding sites in Arabidopsis reveals novel DNA damage regulators. PLoS Genetics, 14, 1-35.
Chen, H., Zou, Y., Shang, Y., Lin, H., Wang, Y., Cai, R. et al. (2008) Firefly luciferase complementation imaging assay for protein-protein interactions in plants. Plant Physiology, 146, 368-376.
Chen, J. (2016) The cell-cycle arrest and apoptotic functions of p53 in tumor initiation and progression. Cold Spring Harbor Perspectives in Medicine, 6, 1-16.
Chen, P., Sjogren, C.A., Larsen, P.B. & Schnittger, A. (2019) A multi-level response to DNA damage induced by aluminium. The Plant Journal, 98, 479-491.
Chen, P., Takatsuka, H., Takahashi, N., Kurata, R., Fukao, Y., Kobayashi, K. et al. (2017) Arabidopsis R1R2R3-Myb proteins are essential for inhibiting cell division in response to DNA damage. Nature Communications, 8, 1-12.
Chen, T. & Wang, J.Y.J. (2000) Establishment of irreversible growth arrest in myogenic differentiation requires the RB LXCXE-binding function. Molecular and Cellular Biology, 20, 5571-5580.
Chen, Z., Higgins, J.D., Hui, J.T.L., Li, J., Franklin, F.C.H. & Berger, F. (2011) Retinoblastoma protein is essential for early meiotic events in Arabidopsis. The EMBO Journal, 30, 744-755.
Ciccia, A. & Elledge, S.J. (2010) The DNA damage response: making it safe to play with knives. Molecular Cell, 40, 179-204.
Clay, D.E. & Fox, D.T. (2021) DNA damage responses during the cell cycle: insights from model organisms and beyond. Genes (Basel), 12, 1882.
Cruz-Ramírez, A., Díaz-Triviño, S., Blilou, I., Grieneisen, V.A., Sozzani, R., Zamioudis, C. et al. (2012) A Bistable circuit involving SCARECROW- RETINOBLASTOMA integrates cues to inform asymmetric stem cell division. Cell, 150, 1002-1015.
Cruz-Ramírez, A., Diaz-trivino, S., Wachsman, G., Du, Y., Arteaga-Vazquez, M., Zhang, H. et al. (2013) A SCARECROW-RETINOBLASTOMA protein network controls protective quiescence in the Arabidopsis root stem cell organizer. PLoS Biology, 11, e1001724.
De Folter, S. & Immink, R.G.H. (2011) Yeast protein-protein interaction assays and screens. Methods in Molecular Biology, 754, 145-165.
De Veylder, L., Beeckman, T., Beemster, G.T.S., De Almeida Engler, J., Ormenese, S., Maes, S. et al. (2002) Control of proliferation, endoreduplication and differentiation by the Arabidopsis E2Fa-DPa transcription factor. The EMBO Journal, 21, 1360-1368.
DeCaprio, J.A. (2009) How the Rb tumor suppressor structure and function was revealed by the study of Adenovirus and SV40. Virology, 384, 274-284.
Desvoyes, B., De Mendoza, A., Ruiz-Trillo, I. & Gutierrez, C. (2014) Novel roles of plant RETINOBLASTOMA-RELATED (RBR) protein in cell proliferation and asymmetric cell division. Journal of Experimental Botany, 65, 2657-2666.
Desvoyes, B., Fernández-marcos, M., Sequeira-mendes, J., Otero, S., Vergara, Z. & Gutierrez, C. (2014) Looking at plant cell cycle from the chromatin window. Frontiers in Plant Science, 5, 369.
Desvoyes, B. & Gutierrez, C. (2020) Roles of plant retinoblastoma protein: cell cycle and beyond. The EMBO Journal, 39, 1-18.
Dick, F.A. & Rubin, S.M. (2013) Molecular mechanisms underlying RB protein function. Nature Reviews. Molecular Cell Biology, 14, 297-306.
Ebel, C., Mariconti, L. & Gruissem, W.W. (2004) Plant retinoblastoma homologues control nuclear proliferation in the female gametophyte. Nature, 429, 776-780.
Engeland, K. (2018) Cell cycle arrest through indirect transcriptional repression by p53: I have a DREAM. Cell Death and Differentiation, 25, 114-132.
Engler, C., Youles, M., Gruetzner, R., Ehnert, T.M., Werner, S., Jones, J.D.G. et al. (2014) A Golden Gate modular cloning toolbox for plants. ACS Synthetic Biology, 3, 839-843.
Flemington, E.K., Speck, S.H. & Kaelin, W.G. (1993) E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Proceedings of the National Academy of Sciences of the United States of America, 90, 6914-6918.
Gentric, N., Masoud, K., Journot, R.P., Cognat, V., Chabouté, M.E., Noir, S. et al. (2020) The f-box-like protein FBL17 is a regulator of DNA-damage response and colocalizes with RETINOBLASTOMA RELATED1 at DNA lesion sites. Plant Physiology, 183, 1295-1305.
Gombos, M., Raynaud, C., Nomoto, Y., Molnár, E., Brik-Chaouche, R., Takatsuka, H. et al. (2023) The canonical E2Fs together with RETINOBLASTOMA-RELATED are required to establish quiescence during plant development. Communications Biology, 6, 1-15.
Gutzat, R., Borghi, L. & Gruissem, W. (2012) Emerging roles of RETINOBLASTOMA-RELATED proteins in evolution and plant development. Trends in Plant Science, 17, 139-148.
Harashima, H. & Sugimoto, K. (2016) Integration of developmental and environmental signals into cell proliferation and differentiation through RETINOBLASTOMA-RELATED 1. Current Opinion in Plant Biology, 29, 95-103.
Helin, K., Harlow, E.D. & Fattaey, A.L. (1993) Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Molecular and Cellular Biology, 13, 6501-6508.
Hirakawa, T., Hasegawa, J., White, C.I. & Matsunaga, S. (2017) RAD54 forms DNA repair foci in response to DNA damage in living plant cells. The Plant Journal, 90, 372-382.
Hirakawa, T. & Matsunaga, S. (2019) Characterization of DNA repair foci in root cells of Arabidopsis in response to DNA damage. Frontiers in Plant Science, 10, 990.
Horvath, B.M., Kourova, H., Nagy, S., Nemeth, E., Magyar, Z., Papdi, C. et al. (2017) Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control. The EMBO Journal, 36, 1261-1278.
Hu, Z., Cools, T. & De Veylder, L. (2016) Mechanisms used by plants to cope with DNA damage. Annual Review of Plant Biology, 67, 439-462.
Ito, M., Araki, S., Matsunaga, S., Itoh, T., Nishihama, R., Machida, Y. et al. (2001) G2/M-phase-specific transcription during the plant cell cycle is mediated by c-Myb-like transcription factors. Plant Cell, 13, 1891-1905.
Ito, M., Iwase, M., Kodama, H., Lavisse, P., Komamine, A., Nishihama, R. et al. (1998) A novel cis-acting element in promoters of plant B-type cyclin genes activates M phase-specific transcription. Plant Cell, 10, 331-341.
Johnston, A.J., Matveeva, E., Kirioukhova, O., Grossniklaus, U. & Gruissem, W. (2008) A dynamic reciprocal RBR-PRC2 regulatory circuit controls Arabidopsis gametophyte development. Current Biology, 18, 1680-1686.
Kastenhuber, E.R. & Lowe, S.W. (2017) Putting p53 in context. Cell, 170, 1062-1078.
Kim, J.H., Ryu, T.H., Lee, S.S., Lee, S. & Chung, B.Y. (2019) Ionizing radiation manifesting DNA damage response in plants: an overview of DNA damage signaling and repair mechanisms in plants. Plant Science, 278, 44-53.
Kobayashi, K., Suzuki, T., Iwata, E., Nakamichi, N., Suzuki, T., Chen, P. et al. (2015) Transcriptional repression by MYB 3R proteins regulates plant organ growth. The EMBO Journal, 34, 1992-2007.
Kurihara, D., Mizuta, Y., Sato, Y. & Higashiyama, T. (2015) ClearSee: a rapid optical clearing reagent for whole-plant fluorescence imaging. Development, 142, 4168-4179.
Lampropoulos, A., Sutikovic, Z., Wenzl, C., Maegele, I., Lohmann, J.U. & Forner, J. (2013) GreenGate - a novel, versatile, and efficient cloning system for plant transgenesis. PLoS One, 8, e83043.
Lang, L., Pettkó-Szandtner, A., Elbasi, H.T., Takatsuka, H., Nomoto, Y., Zaki, A. et al. (2021) The DREAM complex represses growth in response to DNA damage in Arabidopsis. Life Science Alliance, 4, 1-20.
Lanz, M.C., Dibitetto, D. & Smolka, M.B. (2019) DNA damage kinase signaling: checkpoint and repair at 30 years. The EMBO Journal, 38, e101801.
Magyar, Z., Horváth, B., Khan, S., Mohammed, B., Henriques, R., De Veylder, L. et al. (2012) Arabidopsis E2FA stimulates proliferation and endocycle separately through RBR-bound and RBR-free complexes. The EMBO Journal, 31, 1480-1493.
Mahapatra, K. & Roy, S. (2020) An insight into the mechanism of DNA damage response in plants- role of SUPPRESSOR OF GAMMA RESPONSE 1: an overview. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 819-820, 111689.
Nakagami, H., Kawamura, K., Sugisaka, K., Sekine, M. & Shinmyo, A. (2002) Phosphorylation of retinoblastoma-related protein by the cyclin D/cyclin-dependent kinase complex is activated at the G1/S-phase transition in tobacco. Plant Cell, 14, 1847-1857.
Nakamura, A.J., Rao, V.A., Pommier, Y. & Bonner, W.M. (2010) The complexity of phosphorylated H2AX foci formation and DNA repair assembly at DNA double-strand breaks. Cell Cycle, 9, 389-397.
Narasimha, A.M., Kaulich, M., Shapiro, G.S., Choi, Y.J., Sicinski, P. & Dowdy, S.F. (2014) Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. eLife, 3, 1-21.
Ning, Y., Liu, N., Lan, K., Su, Y., Li, L., Chen, S. et al. (2020) DREAM complex suppresses DNA methylation maintenance genes and precludes DNA hypermethylation. Nature Plants, 6, 942-956.
Nisa, M., Eekhout, T., Bergis, C., Pedroza-Garcia, J.A., He, X., Mazubert, C. et al. (2023) Distinctive and complementary roles of E2F transcription factors during plant replication stress responses. Molecular Plant, 16, 1269-1282.
Nisa, M.U., 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. Frontiers in Plant Science, 10, 1-12.
Ogita, N., Okushima, Y., Tokizawa, M., Yamamoto, Y.Y., Tanaka, M., Seki, M. et al. (2018) Identifying the target genes of SUPPRESSOR OF GAMMA RESPONSE 1, a master transcription factor controlling DNA damage response in Arabidopsis. The Plant Journal, 94, 439-453.
Perilli, S., Perez-Perez, J.M., Di Mambro, R., Peris, C.L., Díaz-Triviño, S., Del Bianco, M. et al. (2013) RETINOBLASTOMA-RELATED protein stimulates cell differentiation in the Arabidopsis root meristem by interacting with cytokinin signaling. Plant Cell, 25, 4469-4478.
Polit, J.T., Kaźmierczak, A. & Walczak-Drzewiecka, A. (2012) Cell cycle-dependent phosphorylation of pRb-like protein in root meristem cells of Vicia faba. Protoplasma, 249, 131-137.
Polo, S.E. & Jackson, S.P. (2011) Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes & Development, 25, 409-433.
Prokhorova, E.A., Egorshina, A.Y., Zhivotovsky, B. & Kopeina, G.S. (2020) The DNA-damage response and nuclear events as regulators of nonapoptotic forms of cell death. Oncogene, 39, 1-16.
Pruneda-Paz, J.L.L., Breton, G., Nagel, D.H.H., Kang, S.E.E., Bonaldi, K., Doherty, C.J.J. et al. (2014) A genome-scale resource for the functional characterization of Arabidopsis transcription factors. Cell Reports, 8, 622-632.
Reape, T.J., Molony, E.M. & McCabe, P.F. (2008) Programmed cell death in plants: distinguishing between different modes. Journal of Experimental Botany, 59, 435-444.
Rubin, S.M. (2013) Deciphering the retinoblastoma protein phosphorylation code. Trends in Biochemical Sciences, 38, 12-19.
Sanidas, I., Morris, R., Fella, K.A., Rumde, P.H., Boukhali, M., Tai, E.C. et al. (2019) A code of mono-phosphorylation modulates the function of RB. Molecular Cell, 73, 985-1000.e6.
Surova, O. & Zhivotovsky, B. (2013) Various modes of cell death induced by DNA damage. Oncogene, 32, 3789-3797.
Szurman-Zubrzycka, M., Jędrzejek, P. & Szarejko, I. (2023) How do plants cope with DNA damage? A concise review on the DDR pathway in plants. International Journal of Molecular Sciences, 24, 2404.
Takahashi, N., Ogita, N., Takahashi, T., Taniguchi, S., Tanaka, M., Seki, M. et al. (2019) A regulatory module controlling stress-induced cell cycle arrest in Arabidopsis. eLife, 8, 1-27.
Thévenaz, P., Ruttimann, U.E. & Unser, M. (1998) A pyramid approach to subpixel registration based on intensity. IEEE Transactions on Image Processing, 7, 27-41.
Tsegay, P.S., Lai, Y. & Liu, Y. (2019) Replication stress and consequential instability of the genome and epigenome. Molecules, 24, 1-20.
Vélez-Cruz, R., Manickavinayaham, S., Biswas, A.K., Clary, R.W., Premkumar, T., Cole, F. et al. (2016) RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1. Genes & Development, 30, 2500-2512.
Verkest, A., Abeel, T., Heyndrickx, K.S., Van Leene, J., Lanz, C., Van De Slijke, E. et al. (2014) A generic tool for transcription factor target gene discovery in Arabidopsis cell suspension cultures based on tandemchromatinaffinity purification. Plant Physiology, 164, 1122-1133.
Waterworth, W.M., Wilson, M., Wang, D., Nuhse, T., Warward, S., Selley, J. et al. (2019) Phosphoproteomic analysis reveals plant DNA damage signalling pathways with a functional role for histone H2AX phosphorylation in plant growth under genotoxic stress. The Plant Journal, 100, 1007-1021.
Wildwater, M., Campilho, A., Perez-Perez, J.M., Heidstra, R., Blilou, I., Korthout, H. et al. (2005) The RETINOBLASTOMA-RELATED gene regulates stem cell maintenance in Arabidopsis roots. Cell, 123, 1337-1349.
Williams, A.B. & Schumacher, B. (2016) p53 in the DNA-damage-repair process. Cold Spring Harbor Perspectives in Medicine, 6, 1-16.
Yi, D., Kamei, C.L.A., Cools, T., Vanderauwera, S., Takahashi, N., Okushima, Y. et al. (2014) The Arabidopsis SIAMESE-RELATED cyclin-dependent kinase inhibitors SMR5 and SMR7 regulate the DNA damage checkpoint in response to reactive oxygen species. Plant Cell, 26, 296-309.
Yoshiyama, K., Conklin, P.A., Huefner, N.D. & Britt, A.B. (2009) Suppressor of gamma response 1 (SOG1) encodes a putative transcription factor governing multiple responses to DNA damage. Proceedings of the National Academy of Sciences of the United States of America, 106, 12843-12848.
Zamora-Zaragoza, J., Klap, K., Sánchez-Pérez, J., Vielle-Calzada, J.P. & Scheres, B. (2021) A phosphorylation code regulates the multi-functional protein RETINOBLASTOMA-RELATED1 in Arabidopsis thaliana. BioRxiv.
Zhou, W., Lozano-Torres, J.L., Blilou, I., Zhang, X., Zhai, Q., Smant, G. et al. (2019) A Jasmonate signaling network activates root stem cells and promotes regeneration. Cell, 177, 942-956.e14.