Elena Anatolievna Alekseeva*, Tatiyana Anatolievna Evstyukhina, Vyacheslav Timofeevich Peshekhonov, Irina Igorievna Skobeleva and Vladimir Gennadievich Korolev
Volume5-Issue4
Dates: Received: 2024-02-18 | Accepted: 2024-04-25 | Published: 2024-04-26
Pages: 360-372
Abstract
Reparative chromatin assembly is an important step in maintaining the stability of the genome. Proper chromatin assembly is provided by histone chaperones. Violation of the function of these proteins can lead to the development of various forms of cancer and to a number of hereditary diseases in humans. One of the key processes in the reparative assembly of chromatin is acetylation and deacetylation of histones, complexes NuB4 and RPD3. Results presented in this work demonstrate that inactivation of Rpd3 and Sin3 subunits of the RPD3 complex blocks super activation of RNR3 gene. The phenotypes of rpd3Δ and sin3Δ mutants differ due to different activation of Rad53 kinase in these mutants, which may be due to deacetylation of Rad53 by Rpd3 deacetylase. Our findings revealed that the contribution of deacetylation of Rad53 kinase makes a significant contribution to the regulation hyperactivation RNR complex after UV irradiation. In addition, this work provides indirect evidence that the Him1 protein may participate as a histone chaperone in chromatin repair assembly.
FullText HTML
FullText PDF
DOI: 10.37871/jbres1902
Certificate of Publication

Copyright
© 2024 Alekseeva EA, et al. Distributed under Creative Commons CC-BY 4.0
How to cite this article
Alekseeva EA, Evstyukhina TA, Peshekhonov VT, Skobeleva II, Korolev VG. The Role of the RPD3 Complex of Saccharomyces cerevisiae Yeast in the Activation of UV-Induced Expression of RNR Complex Genes. J Biomed Res Environ Sci. 2024 Apr 26; 5(4): 360-372. doi: 10.37871/jbres1902, Article ID: JBRES1902, Available at: https://www.jelsciences.com/articles/jbres1902.pdf
Subject area(s)
References
- De Koning L, Corpet A, Haber J.E, Almouzni G. Histone chaperones: an escort network regulating histone traffic. Nat Struct Mol Biol. 2007 Nov;14(11):997-1007. doi: 10.1038/nsmb1318. Epub 2007 Nov 5. PMID: 17984962
- Burgess R.J, Zhang Z, Histone chaperones in nucleosome assembly and human disease. Nat. Nat Struct Mol Biol. 2013 Jan;20(1):14-22. doi: 10.1038/nsmb.2461. PMID: 23288364 PMCID: PMC4004355
- Chen C.C, Carson J.J, Feser J, Tamburini B, Zabaronick S, Linger J, Tyler J.K. Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell. 2008 Jul 25;134(2):231-43. doi: 10.1016/j.cell.2008.06.035. PMID: 18662539 PMCID: PMC2610811
- Osley M.A, Shen X. Altering nucleosomes during DNA double-strand break repair in yeast. Trends Genet. 2006 Dec;22(12):671-7. doi: 10.1016/j.tig.2006.09.007. Epub 2006 Sep 25. PMID: 16997415
- Tsukuda T, Fleming A.B, Nickoloff J.A, Osley M.A. Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae. Nature. 2005 Nov 17;438(7066):379-83. doi: 10.1038/nature04148. PMID: 16292314 PMCID: PMC1388271
- Gaillard P.H, Martini E.M, Kaufman P.D, Stillman B, Moustacchi E, Almouzni G. Chromatin assembly coupled to DNA repair: a new role for chromatin assembly factor 1. Cell. 1996 Sep 20;86(6):887-96. doi: 10.1016/s0092-8674(00)80164-6. PMID: 8808624
- Evstyukhina T.A, Alekseeva E.A, Fedorov D.V, Peshekhonov V.T, Korolev V.G. Genetic analysis of the Hsm3 protein function in yeast Saccharomyces cerevisiae NuB4 complex. Genes (Basel). 2021 Jul 17;12(7):1083. doi: 10.3390/genes12071083. PMID: 34356099 PMCID: PMC8307810
- Hu F, Alcasabas A.A, Elledge S.J. Asf1 links Rad53 to control of chromatin assembly. Genes Dev. 2001 May 1;15(9):1061-6. doi: 10.1101/gad.873201. PMID: 11331602 PMCID: PMC312686
- Jasencakova Z, Scharf A.N, Corpet A, Imhof A, Almouzni G, Groth A. Replication stress interferes with histone recycling and predeposition marking of new histones. Mol Cell. 2010 Mar 12;37(5):736-43. doi: 10.1016/j.molcel.2010.01.033. PMID: 20227376
- Das C, Tyler J.K, Churchill M.E. The histone shuffle: Histone chaperones in an energetic dance. Trends Biochem Sci. 2010 Sep;35(9):476-89. doi: 10.1016/j.tibs.2010.04.001. Epub 2010 May 3. PMID: 20444609 PMCID: PMC4004086
- Groth A, Corpet A, Cook AJ, Roche D, Bartek J, Lukas J, Almouzni G. Regulation of replication fork progression through histone supply and demand. Science. 2007;318(5858):1928-31. doi: 10.1126/science.1148992.
- Groth A, Ray-Gallet D, Quivy J.P, Lukas J, Bartek J, Almouzni G. Human Asf1 regulates the flow of S phase histones during replicational stress. Mol Cell. 2005 Jan 21;17(2):301-11. doi: 10.1016/j.molcel.2004.12.018. PMID: 15664198
- Ai X, Parthun M.R. The nuclear Hat1p/Hat2p complex: A molecular link between type B histone acetyltransferases and chromatin assembly. Mol Cell. 2004 Apr 23;14(2):195-205. doi: 10.1016/s1097-2765(04)00184-4. PMID: 15099519
- Poveda A, Pamblanco M, Tafrov S, Tordera V, Sternglanz R., Sendra R. Hif1 is a component of yeast histone acetyltransferase B, a complex mainly localized in the nucleus. J Biol Chem. 2004 Apr 16;279(16):16033-43. doi: 10.1074/jbc.M314228200. Epub 2004 Feb 3. PMID: 14761951
- Qin S, Parthum M.R. Histone H3 and the histone acetyltransferase Hat1 contribute to DNA double-srand break repair. Mol Cell Biol. 2002 Dec;22(23):8353-65. doi: 10.1128/MCB.22.23.8353-8365.2002. PMID: 12417736 PMCID: PMC134061
- Campos E.I, Fillingham J, Li G, Zheng H, Voigt P, Kuo W.H, Seepany H, Gao Z, Day L.A, Greenblatt J.F, Reinberg D. The program for processing newly synthesized histones H3.1 and H4. Nat Struct Mol Biol. 2010 Nov;17(11):1343-51. doi: 10.1038/nsmb.1911. Epub 2010 Oct 17. PMID: 20953179 PMCID: PMC2988979
- Carrozza M.J, Li B, Florens L, Suganuma T, Swanson S.K, Lee K.K, Shia W.J, Anderson S, Yates J, Washburn M.P, Workman J.L. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Cell. 2005 Nov 18;123(4):581-92. doi: 10.1016/j.cell.2005.10.023. PMID: 16286007
- Keogh M.C, Kurdistani S.K, Morris S.A, Ahn S.H, Podolny V, Collins S.R, Schuldiner M, Chin K, Punna T, Thjmpson N.J, Boone C, Emili A, Weissman J.S, Hughes T.R, Strahl B.D, Grunstein M, Greenblatt J.F, Buratowski S, Krogan N.J. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell. 2005 Nov 18;123(4):593-605. doi: 10.1016/j.cell.2005.10.025. PMID: 16286008
- Chen X-F, Kuryan B, Kitada T, Tran N, Li J-Y, Kurdistani S, Grunstein M, Li B, Carey M. The Rpd3 core complex is a chromatin stabilization module. Curr Biol. 2012 Jan 10;22(1):56-63. doi: 10.1016/j.cub.2011.11.042. Epub 2011 Dec 15. PMID: 22177115 PMCID: PMC3758238
- Florens L, Carrozza M.J, Swanson S.K, Fournier M, Coleman M.K, Workman J.L, Washburn M.P. Analyzing chromatin remodeling complexes using shotgun proteomics and normalized spectral abundance factors. Methods. 2006 Dec;40(4):303-11. doi: 10.1016/j.ymeth.2006.07.028. PMID: 17101441 PMCID: PMC1815300
- Li B, Carey M, Workman J.L. The role of chromatin during transcription. Cell. 2007 Feb 23;128(4):707-19. doi: 10.1016/j.cell.2007.01.015. PMID: 17320508
- Bowdish K.S, Mitchell A. Bipartite structure of an early meiotic upstream activation sequence from Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2172-81. doi: 10.1128/mcb.13.4.2172-2181.1993. PMID: 8455605 PMCID: PMC359538
- Vidal M, Strich R.E, Gaber R.F. RPD1 (SIN3/UME4) is required for maximal activation and repression of diverse yeast genes. Mol Cell Biol. 1991 Dec;11(12):6306-16. doi: 10.1128/mcb.11.12.6306-6316.1991. PMID: 1944290 PMCID: PMC361824
- Yoshimoto H, Yamashita I. The Saccharomyces cerevisiae GAM2/SIN3 protein plays a role in both activation and repression of transcription. Mol Gen Genet. 1992 May;233(1-2):327-30. doi: 10.1007/BF00587597. PMID: 1603074
- Kasten M.M, Dorland S, Stillman D.J. A large protein complex containing the yeast Sin3p and Rpd3p transcriptional regulators. Mol Cell Biol. 1997 Aug;17(8):4852-8. doi: 10.1128/MCB.17.8.4852. PMID: 9234741 PMCID: PMC232337
- Wolffe A.P. Histone acetylase: a regulator of transcription. Science. 1996 Apr 19;272(5260):371-2. doi: 10.1126/science.272.5260.371. PMID: 8602525
- Esposito M.S, Brown J.T. Conditional hypo-recombination mutants of three REC genes of Saccharomyces cerevisiae. Curr Genet. 1990 Jan;17(1):7-12. doi: 10.1007/BF00313242. PMID: 2178786
- Dora E.G, Rudin N, Martell J.R, Esposito M.S, Ramírez R.M. RPD3 (REC3) mutations affect mitotic recombination in Saccharomyces cerevisiae. Curr Genet. 1999 Mar;35(2):68-76. doi: 10.1007/s002940050434. PMID: 10079324
- Scott K.L, Plon S.E. Loss of Sin3/Rpd3 histone deacetylase restores the DNA damage response in checkpoint-deficient strains of Saccharomyces cerevisiae. Mol Cell Biol. 2003 Jul;23(13):4522-31. doi: 10.1128/MCB.23.13.4522-4531.2003. PMID: 12808094 PMCID: PMC164854
- Debacker K, Frizzell A, Gleeson O, Kirkham-McCarthy L, Mertz T, Lahue R.S. Histone deacetylase complexes promote trinucleotide repeat expansions. PLoS Biol. 2012 Feb;10(2):e1001257. doi: 10.1371/journal.pbio.1001257. Epub 2012 Feb 21. PMID: 22363205 PMCID: PMC3283555
- Alekseeva E.A, Evstyukhina T.A, Peshekhonov V.T, Korolev V.G. Participation of the HIM1 gene of yeast Saccharomyces cerevisiae in the error-free branch of post-replicative repair and role Polη in him1-dependent mutagenesis. Curr Genet. 2021 Feb;67(1):141-151. doi: 10.1007/s00294-020-01115-6. Epub 2020 Oct 31. PMID: 33128582 PMCID: PMC7886746
- Tao R, Xue H, Zhang J, Liu J, Deng H, Chen Y-G. Deacetylase Rpd3 facilitates checkpoint adaption by preventing Rad53 overactivation, Mol Cell Biol. 2013 Nov;33(21):4212-24. doi: 10.1128/MCB.00618-13. Epub 2013 Aug 26. PMID: 23979600 PMCID: PMC3811893
- Zakharov I.A, Kozhin S.A, Kozhina T.A, Fedorova I.V. Sbornik metodik po genetike drozhzhei-sakharomitsetov, Methods of yeast Saccharomyces cerevisiae genetics. Leningrad: Nauka. 1984. p144.
- Lebovka I.Yu, Kozhina T.N, Fedorova I.V, Peshekhonov V.T, Evstyukhina T.A, Chernenkov A.Yu, V.G. Korolev V.G. Sin3 histone deacetylase controls level of spontaneous and UV induced mutagenesis in yeast Saccharomyces cerevisiae. Genetika. 2014 Jan;50(1):5-11. PMID: 25711007
- Chernenkov A.Y, Gracheva L.M, Evstyukhina T.A, Koval’tsova S.V, Peshekhonov V.T, Fedorova I.V, Korolev V.G. HSM3 gene interaction with epistatic RAD6 group genes in yeasts Saccharomyces cerevisiae. Genetika. 2012 Feb;48(2):160-7. PMID: 22567994
- Kovaltzova S.V, Korolev V.G. The Saccharomyces cerevisiae yeast strain for testing environmental mutagens based on the interaction between rad2 and him1 mutations. Genetika. 1996 Mar;32(3):366-72. PMID: 8723629
- Lea D.E, Coulson C.A. The distribution of the numbers of mutants in bacterial populations. J Genet. 1949 Dec;49(3):264-85. doi: 10.1007/BF02986080. PMID: 24536673
- Khromov-Borisov NN, Saffi J, Henriques JAP. Perfect order plating: Principal and applications. TTO. 2002;1TO2638.
- Fedorova I.V, Kovaltzova S.V, Gracheva L.M, Evstyuhina T.A, Korolev V.G. Requirement of HSM3 gene for spontaneous mutagenesis in Saccharomyces cerevisiae. Mutat Res. 2004 Oct 4;554(1-2):67-75. doi: 10.1016/j.mrfmmm.2004.03.003. PMID: 15450405
- Hanway D, Ghin J.K, Xia G, Oshiro G, Winzeler E.A, Romesberg F.E. Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10605-10. doi: 10.1073/pnas.152264899. Epub 2002 Jul 29. PMID: 12149442 PMCID: PMC124988
- Fedorova I.V, Gracheva L.M, Kovaltzova S.V, Evstuhina T.A, Alekseev S.Y, Korolev V.G. The yeast HSM3 gene acts in one of the mismatch repair pathways. Genetics. 1998 Mar;148(3):963-73. doi: 10.1093/genetics/148.3.963. PMID: 9539417 PMCID: PMC1460053
- Kelberg E.P, Kovaltsova S.V, Alekseev S.Yu, Fedorova I.V, Gracheva L.M, Evstukhina T.A, Korolev V.G. HIM1, a new yeast Saccharomyces cerevisiae gene playing a role in control of spontaneous and induction mutagenesis. Mutat Res. 2005 Oct 15;578(1-2):64-78. doi: 10.1016/j.mrfmmm.2005.03.003. PMID: 15885712
- Keck K.M, Pemberton L.F. Histone chaperones link histone nuclear import and chromatin assembly. Biochim Biophys Acta. 2012 Mar;1819(3-4):277-89. doi: 10.1016/j.bbagrm.2011.09.007. Epub 2011 Oct 8. PMID: 22015777 PMCID: PMC3272145
- Evstyukhina T.A, Alekseeva E.A, Peshekhonov V.T, Skobeleva I.I, Korolev V.G. The role of chromatin assembly factors in induced mutagenesis at low levels of DNA damage. Genes (Basel). 2023 Jun 10;14(6):1242. doi: 10.3390/genes14061242. PMID: 37372422 PMCID: PMC10298286
- Sun Z, Hsiao J, Fay D.S, Stern D.F. Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. Science. 1998 Jul 10;281(5374):272-4. doi: 10.1126/science.281.5374.272. PMID: 9657725
- Sharma V.M, Tomar R.S, Dempsey A.E, Reese J.C. Histone deacetilases Rpd3 and Hos2 regulate the transcriptional activation of DNA damage inducible genes. Mol Cell Biol. 2007 Apr;27(8):3199-210. doi: 10.1128/MCB.02311-06. Epub 2007 Feb 12. PMID: 17296735 PMCID: PMC1899941