Group of RNA epigenetics and genome stability

Alexey S. Ruzov
Dr.Sci. (Biology)
Head of the group
INBI, room 211

 

Телефон (499) 135-20-69
E-Mail alexey.ruzov@gmail.com

General information

R-loops are nucleic acid structures formed by an RNA/DNA hybrid and an unpaired single stranded DNA that contribute to a number of important biological processes in mammalian cells. Our recent results highlighted RNA N6-methyladenosine (m6A) as an integral component of these structures pivotal for regulation of their stability and contributing to various aspects of their biology. Together with complementary studies, this work opened a new avenue for studying RNA modifications as novel determinants of chromatin structure and genome stability representing an additional layer of epigenetic regulation of gene expression. As these findings have multiple implications for understanding the mechanisms of epigenetic gene regulation, maintenance of genome integrity and pathogenesis of R-loop-related diseases, our current research programme is focused on deciphering the roles of RNA modifications in chromatin regulation and R-loops metabolism in the context of cellular differentiation and tumorigenesis.

Selected publications

  1. Abakir A, Ruzov A. (2021) SWI/SNF complexes as determinants of R-loop metabolism. Nat Genet. 53, 940–941.
  2. Blythe M, Kocer A, Rubio-Roldan A, Giles T, Abakir A, Ialy-Radio C, Wheldon LM, Bereshchenko O, Bruscoli S, Kondrashov A, Drevet JR, Emes RD, Johnson AD, McCarrey JR, Gackowski D, Olinski R, Cocquet J, Garcia-Perez JL, Ruzov A. (2021) LINE-1 transcription in round spermatids is associated with accretion of 5-carboxylcytosine in their open reading frames. Commun Biol. 4, 691.
  3. Abakir A, Alenezi F, Ruzov A. (2021) Analysis of 5-carboxylcytosine distribution using DNA immunoprecipitation. Methods Mol Biol. 2198:311-319 (book chapter).
  4. Abakir A, Ruzov A. (2021) Detection of low-abundance DNA modifications using signal amplification-based immunocytochemistry. Methods Mol Biol. 2198:169-181 (book chapter).
  5. Lowe P, Olinski R, Ruzov A. (2021) Evidence for noncytosine epigenetic DNA modifications in multicellular eukaryotes: an overview. Methods Mol Biol. 2198:15-25 (book chapter).
  6. Eleftheriou M, Ruzov A. (2021) Modified forms of cytosine in eukaryotes: DNA (de)methylation and beyond. Methods Mol Biol. 2198:3-13 (book chapter).
  7. Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, Rubio-Roldan A, Li M, Eleftheriou M, Crutchley J, Flatt L, Young L, Gaffney DJ, Denning C, Dalhus B, Emes RD, Gackowski D, Corrêa IR, Garcia-Perez JL, Klungland A, Gromak N, Ruzov A. (2020) N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet. 52, 48–55. Featured on the front page and in News & Views: Marnef A, Legube G. m6A RNA modification as a new player in R-loop regulation. (2020) Nat Genet. 52, 27–28.
  8. Gackowski D, Gawronski M, Kerr C, Radivoyevitch T, Zarakowska E, Starczak M, Abakir A, Ruzov A, Maciejewski JP, Olinski R. (2020) 5-Formylcytosine and 5-hydroxymethyluracil as surrogate markers of TET2 and SF3B1 mutations in myelodysplastic syndrome, respectively. Haematologica. 105:e213-e215.
  9. Yakovlev I, Gackowski D, Abakir A, Viejo M, Ruzov A, Olinski R, Starczak M, Fossdal CG, Krutovsky K. (2019) Mass spectrometry reveals the presence of specific set of epigenetic DNA modifications in the Norway spruce genome. Sci. Rep. 9(1):19314. co-corresponding author.
  10. Gulaia V, Kumeiko V, Shved N, Cicinskas E, Rybtsov S, Ruzov A, Kagansky A. (2018) Molecular mechanisms governing the stem cell’s fate in brain cancer: factors of stemness and quiescence. Front. Cell. Neurosci. 12:388. co-corresponding author.
  11. Stöger R, Ruzov A. (2018). Editorial: Beyond CpG methylation: new modifications in eukaryotic DNA. Front. Cell Dev. Biol. 6:87.
  12. Jessop P, Ruzov A, Gering M. (2018). Developmental functions of the dynamic DNA methylome and hydroxymethylome in the mouse and zebrafish: similarities and differences. Front. Cell Dev. Biol. 6:27. co-corresponding author.
  13. Ramsawhook A, Ruzov A, Coyle B. (2018). Wilms’ Tumour protein 1 and enzymatic oxidation of 5-methylcytosine in brain tumours: potential perspectives. Front. Cell Dev. Biol. 6:26 co-corresponding author.
  14. Moler ERV, Abakir A, Eleftheriou M, Johnson JS, Krutovsky KV, Lewis LC, Ruzov A, Whipple AV, Rajora OP (2018) Population epigenomics: advancing understanding of phenotypic plasticity, acclimation, adaptation and diseases. In: Om P. Rajora (ed.), Population Genomics: Concepts, Approaches and Applications. Springer International Publishing AG, DOI: 10.1007/13836_2018_59. Part of ISSN: 2364-6764. (book chapter).
  15. Ramsawhook AH, Lewis LC, Eleftheriou M, Abakir A, Durczak P, Markus R, Rajani S, Hannan NRF, Coyle B, Ruzov A. (2017). Immunostaining for DNA modifications: computational analysis of confocal images. J Vis Exp. 127, e56318, doi:10.3791/56318.
  16. Lewis LC, Lo PC, Foster JM, Dai N, Corrêa IR Jr, Durczak PM, Duncan G, Ramsawhook A, Aithal GP, Denning C, Hannan NRF, Ruzov A. (2017). Dynamics of 5-carboxylcytosine during hepatic differentiation: potential general role for active demethylation by DNA repair in lineage specification.  Epigenetics, 12(4):277-286. Cover image.
  17. Ramsawhook A, Lewis L, Coyle B, Ruzov A. (2017). Medulloblastoma and ependymoma cells display increased levels of 5-carboxylcytosine and elevated TET1 expression. Clin Epigenetics, 9:18.
  18. Abakir A, Wheldon L, Johnson AD, Laurent P, Ruzov A. (2016). Detection of modified forms of cytosine using sensitive immunohistochemistry. J Vis Exp. 114, e54416, doi:10.3791/54416.
  19. Abakir A, Wheldon LM, Ruzov A. (2016) Immunohistochemical detection of oxidized forms of 5-methylcytosine in embryonic and adult brain tissue. In: Karpova N. (ed.) Epigenetic Methods in Neuroscience Research. Neuromethods, vol 105, Humana Press, New York, NY. DOI: 10.1007/978-1-4939-2754-8_8; ISBN 978-1-4939-2753-1. (book chapter).
  20. Eleftheriou M, Jimenez Pascual A, Wheldon LM, Perry C, Abakir A, Arora A, Johnson AD, Auer DT,  Ellis IO, Madhusudan S, Ruzov A (2015). 5-Carboxylcytosine levels are elevated in human breast cancers and gliomas. Clin Epigenetics 7(1):88.
  21. Ciccone NA, Mwangi W, Ruzov A, Smith LP, Butter C, Nair V. (2014). A B-cell targeting virus disrupts potentially protective genomic methylation patterns in lymphoid tissue by increasing global 5-hydroxymethylcytosine levels. Vet Res. 45:108.
  22. Tsenkina Y, Ruzov A, Gliddon C, Horsburgh K, De Sousa PA.(2014). White matter tract and glial-associated changes in 5-hydroxymethylcytosine following chronic cerebral hypoperfusion. Brain Res.1592:82-100.
  23. Wheldon LM, Abakir A, Ferjentsik Z, Dudnakova T, Strohbuecker S, Christie D, Dai N, Guan S, Foster JM, Corrêa IR Jr, Loose M, Dixon JE, Sottile V, Johnson AD, Ruzov A. (2014) Transient accumulation of 5-carboxylcytosine indicates involvement of active demethylation in lineage specification of neural stem cells. Cell Rep. 7(5):1353-61.
  24. Jaber-Hijazi F, Lo PJ, Mihaylova Y, Foster JM, Benner JS, Tejada Romero B, Chen C, Malla S, Solana J, Ruzov A, Aboobaker A. (2013). Planarian MBD2/3 is required for adult stem cell pluripotency independently of DNA methylation. Dev Biol. 384(1):141-53.
  25. Alioui A, Wheldon L, Abakir A, Ferjentsik Z, Johnson AD, Ruzov A. (2012). 5-Carboxylcytosine is localized to euchromatic regions in the nuclei of follicular cells in axolotl ovary. Nucleus. 3 (6), 565-9.
  26. Almeida R D, Loose M, Sottile V, Matsa E, Denning C, Young L; Johnson AD, Gering M, Ruzov A. (2012). 5-Hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development. Epigenetics. 7 (4), 383-9. Cover image.
  27. Almeida R D, Sottile V, Loose M, De Sousa P, Johnson AD, Ruzov A. (2012). Semiquantitative immunohistochemical detection of 5-hydroxymethylcytosine reveals conservation of its tissue distribution between amphibians and mammals. Epigenetics. 7 (2), 137-40. Cover image.
  28. Ruzov A, Tsenkina Y, Serio A, Dudnakova T, Fletcher J, Bai Y, Chebotareva T, Pells S, Hannoun Z, Sullivan G, Chandran S, Hay D, Bradley M, Wilmut I and De Sousa PA. (2011). Lineage specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development. (12 July 2011); Cell Res. 21, 1332-1342 co-corresponding author.
  29. Nestor C, Ruzov A, Meehan R, Dunican D. (2010). Enzymatic approaches and bisulfite sequencing cannot distinguish between 5-methylcytosine and 5-hydroxymethylcytosine in DNA. Biotechniques. 48(4):317-9.
  30. Ruzov A, Shorning B, Dunican D, Leonhardt H, Mortusewicz O and Meehan RR. (2009). MBD4 and MLH1 are required for apoptotic induction in xDNMT1-depleted embryos. Development, 136(13):2277-86. Featured in Research Highlight: How DNMT1 mediates between repair and death.
  31. Ruzov A, Savitskaya E, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Chekanov N, Minghui L, Dunican DS, Prokhortchouk E, Pennings S and Meehan RR. (2009). The non-methylated DNA binding function of Kaiso is not required in early Xenopus laevis development. Development, 136(5):729-38. Featured in Research Highlight: Kaiso role in a DNA bind.
  32. Ruzov A, Hackett JA, Reddington JP, Prokhortchouk A, Madej MJ, Dunican DS, Prokhortchouk E, Pennings S and Meehan RR. (2009). The interaction of xKaiso with xTcf3: a revised model for integration of epigenetic and Wnt-signalling pathways. Development, 136(5):723-7. Featured in Research Highlight: Kaiso role in a DNA bind.
  33. Dunican DS, Ruzov A, Hackett JA, and Meehan RR. (2008). xDnmt1 regulates transcriptional silencing in pre-MBT Xenopus embryos independently of its catalytic function. Development, 135(7):1295-302. Featured in Research Highlight: Dnmt1: a direct transcription repressor?
  34. Meehan RR, Dunican DS, Ruzov A, Pennings S. (2005). Epigenetic silencing in embryogenesis. Exp Cell Res. 309:241-9. Cover image.
  35. Ruzov A, Dunican DS, Prokhortchouk A, Pennings S, Stancheva I, Prokhortchouk E, Meehan RR. (2004). Kaiso is a genome-wide repressor of transcription that is essential for amphibian development. Development. 131(24):6185-94. Featured in Research Highlight: Staying silent in early development.
  36. Alipov ED, Tyrsina EG, Sarimov RM, Ruzov AS, Prokhortsuk EB. (2004). Acquired radioresistance of progeny of irradiated cells is accompanied by rearrangements in chromatin organization. Radiats Biol Radioecol. 44(2):188-97.
  37. Ruzov AS, Mertsalov IB, Meehan R, Kiselev SL, Buchman VL, Korobko IV (2004). Cloning and developmental expression of MARK/Par-1/MELK-related protein kinase xMAK-V in Xenopus laevis. Dev Genes and Evol, 214:139-143.
  38. Smirnov AS, Ruzov AS, Budanov AV, Prokhortchouk AV, Ivanov AV, Prokhortchouk EB. (2001) High constitutive level of NF-kappaB is crucial for viability of adenocarcinoma cells. Cell Death Differ 8(6):621-30.
  39. Prokhorchuk AV, Aĭtkhozhina DS, Sablina AA, Ruzov AS, Prokhorchuk EB. (2001) KAISO–a new member of the BTB/POZ family specifically binds to methylated DNA sequences. Genetika. 37(6):737-44.
  40. Prokhortchouk A, Hendrich B, Jorgensen H, Ruzov A, Wilm M, Georgiev G, Bird A, Prokhortchouk E (2001) The p120 catenin partner Kaiso is a DNA methylation-dependent transcriptional repressor. Genes Dev 15(13):1613-18.
  41. Prokhorchuk AV, Ruzov AS. (2000). Genome methylation and its role in functioning of the eukaryotic organism. Genetika. 36(11):1475-86.
  42. Smirnov AS, Budanov AV, Ruzov AS, Ivanov AV, Prokhorchuk AV, Gnuchev NV, Prokhorchuk EB. (2000). A high constitutive level of NF-kappa B is necessary for viability of murine adenocarcinoma cells–possible role of p53. Mol Biol (Mosk). 34(5):775-82.
  43. Smirnov AS, Ruzov AS, Gnuchev NV, Prokhorchuk EB. (2000). Mechanisms maintaining high constitutive levels of NF-kappa B in murine adenocarcinoma cells. Dokl Biochem. 373(1-6):148-9.
  44. Ruzov AS, Georgiev GP, Prokhorchuk EB (2000) Functional characteristics of the promoter region of the tag7/PGRP gene in KSML0, KSML100 murine mammary adenocarcinoma cell lines and VMR liver. Genetika 36(5):636-6434.
  45. Prokhortchouk EB, Prokhortchouk AV, Rouzov AS, Kiselev SL, Lukanidin EM, Georgiev GP (1998) A minisatellite “core” element constitutes a novel, chromatin-specific activator of mts1 gene transcription. J Mol Biol 280(2):227-2363.
  46. Akopov SB, Nikolaev LG, Tyrsin OYu, Ruzov AS, Sverdlov ED. (1997). 14 sequences from Chinese hamster genome preferentially binding to the nuclear matrix. Bioorg Khim. 23(9):727-31.

Books, Edited

  1. Ruzov A, Gering M. (eds) DNA Modifications: Methods and Protocols. Methods in Molecular Biology, vol 2198, Humana, New York, NY, (2021); DOI: 10.1007/978-1-0716-0876-0; ISBN 978-1-07-160875-3.
  2. Aguilera A, Ruzov A. (eds) R-loops: Methods and Protocols. Methods in Molecular Biology, in press, scheduled for publication: June 2022.