Sergei Mirkin

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Sergei Mirkin
BornSeptember 29, 1956
Moscow, Russia
Alma materMoscow State University (BS/MS), Russian Academy of Sciences Institute of Molecular Genetics (Ph.D.)
Known forGenome instability
Scientific career
FieldsBiology, genomics
InstitutionsTufts University

Sergei Mirkin (born September 29, 1956) is a Russian-American biologist who studies genome instability mediated by repetitive DNA during DNA replication and transcription.[1] He is a professor of Genetics and Molecular Biology and holds the White Family Chair in Biology at Tufts University.[2]

Early life and education

Mirkin was born in Moscow, Russia. His father was a professional violin player and music entrepreneur who passed away when Mirkin was only 5 years old. His mother gave up playing cello and became an engineer to provide for the family. His passion for biology began to flourish during his time attending High School 135 which specialized in biology. He went on to attend Moscow State University, where he earned both a Bachelor of Science and a Master of Science degree in Genetics.[2] He graduated from the five-year BS/MS program in 1978, after which he went on to pursue a Ph.D. in Molecular Biology at the Russian Academy of Sciences’ Institute of Molecular Genetics.[3]

Academic career

Mirkin earned his Ph.D. in Molecular Biology from the Russian Academy of Sciences in 1983 under the supervision of Roman B. Khesin, a leading molecular biologist. He later described his formative years in the Khesin lab in his essay, “Thinking of R.B. Khesin”.[4] By studying conditionally lethal mutants of  DNA gyrase, he established a fundamental interplay between DNA supercoiling and transcription in E. coli.[5] After earning his Ph.D., Mirkin conducted his postdoctoral studies at the Institute of Molecular Genetics, Russian Academy of Sciences with Maxim Frank-Kamenetskii, a leading Russian biophysicist. This work culminated with the discovery of the three-stranded H-DNA structure.[6] Mirkin came to the US as a Fogarty International Fellow in 1989 and joined the faculty of the Department of Genetics at University of Illinois at Chicago (UIC) in 1990.[7] He worked at UIC until 2006 rising to the rank of Professor of Biochemistry and Molecular Genetics. In 2007, he joined Tufts University as a professor and the White Family Chair in Biology.[2]

Scientific research

Mirkin’s major contributions to science include discovering of the first multi-stranded DNA structure (H-DNA);[6] detection of dynamic non-B DNA structures, including DNA cruciforms and triplexes in vivo;[8] establishing that structure-prone DNA repeats stall DNA replication driving their expansions that are responsible for numerous hereditary diseases in humans;[9] and unraveling the mechanisms and consequences of transcription-replication collisions in vivo.[10]

model of H-DNA cruciform

Currently, the Mirkin lab continues studying genome structure and function from two perspectives: firstly, the mechanisms responsible for the instability of DNA repeats implicated in human disease, secondly, the role of transcription-replication collisions in genome instability and thirdly the mechanisms of genome instability mediated at interstitial telomeric sequences.[1]

Selected publications

  • Mirkin SM, Lyamichev VI, Drushlyak KN, Dobrynin VN, Filippov SA, Frank-Kamenetskii MD (1987) DNA H form requires a homopurine-homopyrimidine mirror repeat. Nature 330: 495-497.[11]
  • Dayn A, Malkhosyan S, Mirkin SM (1992) Transcriptionally driven cruciform formation in vivo. Nucleic Acids Res. 20: 5991-5997.[8]
  • Samadashwily GM, Dayn A, Mirkin SM (1993) Suicidal nucleotide sequences for DNA polymerization. EMBO J. 12: 4975-4983.[12]
  • Frank-Kamenetskii MD, Mirkin SM (1995) Triplex DNA structures. Annu Rev Biochem 64: 65-95.[6]
  • Cox R, Mirkin SM (1997) Characteristic enrichment of DNA repeats in different genomes. Proc Natl Acad Sci USA 94: 5237-5242.[13]
  • Samadashwily GM, Raca G, Mirkin SM (1997) Trinucleotide repeats affect DNA replication in vivo. Nature Genet 17: 298-304.[14]
  • Krasilnikova MM, Samadashwily GM, Krasilnikov AS, Mirkin SM (1998) Transcription through a simple DNA repeat blocks replication elongation. EMBO J 17: 5095-5102.[15]
  • Krasilnikova MM, Mirkin SM (2004) Replication stalling at Friedreich’s ataxia (GAA)n repeats in vivo. Mol Cell Biol 24: 2286-2295.[16]
  • Mirkin EV, Mirkin SM (2005) Mechanisms of transcription-replication collisions in bacteria. Mol Cell Biol 25: 888-895.[17]
  • Mirkin EV, Mirkin SM (2007) Replication fork stalling and natural impediments. Microbiol Mol Biol Rev 71: 13-35.[18]
  • Mirkin SM (2007) Expandable DNA Repeats and Human Disease. Nature 447: 932-940.[19]
  • Voineagu I, Narayanan V, Lobachev KS, Mirkin SM (2008) Replication stalling at unstable inverted repeats: Interplay between DNA hairpins and fork stabilizing proteins. Proc Natl Acad Sci USA 105: 9936-9941.[20]
  • Voineagu I, Surka CF, Shishkin AA, Krasilnikova MM, Mirkin SM (2009) Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility. Nat Struct Mol Biol 16: 226-228.[9]
  • Shishkin AA, Voineagu I, Matera R, Cherng N, Chernet BT, Krasilnikova MM, Narayanan V, Lobachev KS, Mirkin SM (2009) Large-scale expansions of Friedreich's ataxia GAA repeats in yeast. Mol Cell 35: 82-92.[21]
  • Shah KA, Shishkin AA, Voineagu I, Pavlov YI, Shcherbakova PV, Mirkin SM (2012) Role of DNA polymerases in repeat-mediated genome instability. Cell Rep 2: 1088-1095.[22]
  • Aksenova AY, Greenwell PW, Dominska M, Shishkin AA, Kim JC, Petes TD, Mirkin SM (2013) Genome rearrangements caused by interstitial telomeric sequences in yeast. Proc Natl Acad Sci USA 110: 19866-19871.[23]
  • Kim JC, Harris ST, Dinter T, Shah KA, Mirkin SM (2017) The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats. Nat Struct Mol Biol 24: 55-60.[24]
  • Neil AJ, Liang MU, Khristich AN, Shah KA, Mirkin SM (2018) RNA-DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication. Nucleic Acids Res 46: 3487-3497.[25]
  • Kononenko AV, Ebersole T, Vasquez KM, Mirkin SM (2018) Mechanisms of genetic instability caused by (CGG)n repeats in an experimental mammalian system. Nat Struct Mol Biol 25: 669-676.[26]
  • Khristich AN, Armenia JF, Matera RM, Kolchinski AA, Mirkin SM (2020) Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability. Proc Natl Acad Sci USA 117: 1628-1637[27]
  • Neil AJ, Hisey JA, Quasem I, McGinty RJ, Hitczenko M, Khristich AN, Mirkin SM (2021) Replication-independent instability of Friedreich's ataxia GAA repeats during chronological aging. Proc Natl Acad Sci USA 118: e2013080118.[28]
  • Matos-Rodrigues G, van Wietmarschen N, Wu W, Tripathi V, Koussa NC, Pavani R, Nathan WJ, Callen E, Belinky F, Mohammed A, Napierala M, Usdin K, Ansari AZ, Mirkin SM, Nussenzweig A. (2022) S1-END-seq reveals DNA secondary structures in human cells. Mol Cell 22: 1097-2765.[29]
  • Masnovo C, Lobo AF, Mirkin SM (2022) Replication dependent and independent mechanisms of GAA repeat instability. DNA Repair 118: e103385.[30]

Awards and honors

  • Co-organizer, 6th International Conference on Unstable Microsatellites and Human Disease, 3 Costa Rica, 2009[2]
  • Editor-in-Chief, Current Opinions in Genetics and Development, 2010-2013[2]
  • Chair, FASEB Summer Research Conference “Dynamic DNA Structures in Biology”, Itasca, USA, 2014[31]
  • Chair, Gordon Research Conference “DNA Damage, Mutation & Cancer”, Ventura, USA, 2016[32]
  • Keynote Speaker at FASEB Summer Research Conference “Dynamic DNA Structures in Biology”, Saxon River, USA, 2016[2]
  • Keynote Speaker, 19th Annual Midwest DNA Repair Symposium, Dayton, USA, 2017[33]
  • Keynote Speaker, Gordon Research Seminar "Mutagenesis", Newry, USA, 2018[34]
  • Distinguished Senior Scholar Award, Tufts University, 2020[35]

References

  1. ^ a b "Mirkin Lab | Department of Biology". as.tufts.edu. Retrieved 2022-11-08.
  2. ^ a b c d e f "Sergei Mirkin | Department of Biology". as.tufts.edu. Retrieved 2022-11-08.
  3. ^ "Sergei Mirkin – Bio". facultyprofiles.tufts.edu. Retrieved 2022-11-08.
  4. ^ "Thinking of R.B. Khesin - ProQuest". www.proquest.com. ProQuest 760104752. Retrieved 2022-11-08.
  5. ^ Krasilnikov, Andrey S.; Podtelezhnikov, Alexei; Vologodskii, Alexander; Mirkin, Sergei M. (1999-10-08). "Large-scale effects of transcriptional DNA supercoiling in Vivo11Edited by I. Tinoco". Journal of Molecular Biology. 292 (5): 1149–1160. doi:10.1006/jmbi.1999.3117. ISSN 0022-2836. PMID 10512709.
  6. ^ a b c Frank-Kamenetskii, M. D.; Mirkin, S. M. (1995). "Triplex DNA structures". Annual Review of Biochemistry. 64: 65–95. doi:10.1146/annurev.bi.64.070195.000433. ISSN 0066-4154. PMID 7574496.
  7. ^ "ORCID". orcid.org. Retrieved 2022-11-08.
  8. ^ a b Dayn, A; Malkhosyan, S; Mirkin, S M (1992-11-25). "Transcriptionally driven cruciform formation in vivo". Nucleic Acids Research. 20 (22): 5991–5997. doi:10.1093/nar/20.22.5991. ISSN 0305-1048. PMC 334465. PMID 1461732.
  9. ^ a b Voineagu, Irina; Surka, Christine F.; Shishkin, Alexander A.; Krasilnikova, Maria M.; Mirkin, Sergei M. (February 2009). "Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility". Nature Structural & Molecular Biology. 16 (2): 226–228. doi:10.1038/nsmb.1527. ISSN 1545-9985. PMC 2837601. PMID 19136957.
  10. ^ Mirkin, Ekaterina V.; Castro Roa, Daniel; Nudler, Evgeny; Mirkin, Sergei M. (2006-05-09). "Transcription regulatory elements are punctuation marks for DNA replication". Proceedings of the National Academy of Sciences. 103 (19): 7276–7281. Bibcode:2006PNAS..103.7276M. doi:10.1073/pnas.0601127103. ISSN 0027-8424. PMC 1464333. PMID 16670199.
  11. ^ Mirkin, S. M.; Lyamichev, V. I.; Drushlyak, K. N.; Dobrynin, V. N.; Filippov, S. A.; Frank-Kamenetskii, M. D. (December 1987). "DNA H form requires a homopurine–homopyrimidine mirror repeat". Nature. 330 (6147): 495–497. Bibcode:1987Natur.330..495M. doi:10.1038/330495a0. ISSN 1476-4687. PMID 2825028. S2CID 4360764.
  12. ^ Samadashwily, G M; Dayn, A; Mirkin, S M (1993-12-15). "Suicidal nucleotide sequences for DNA polymerization". The EMBO Journal. 12 (13): 4975–4983. doi:10.1002/j.1460-2075.1993.tb06191.x. ISSN 0261-4189. PMC 413758. PMID 8262040.
  13. ^ Cox, R.; Mirkin, S. M. (1997-05-13). "Characteristic enrichment of DNA repeats in different genomes". Proceedings of the National Academy of Sciences of the United States of America. 94 (10): 5237–5242. Bibcode:1997PNAS...94.5237C. doi:10.1073/pnas.94.10.5237. ISSN 0027-8424. PMC 24662. PMID 9144221.
  14. ^ Samadashwily, George M.; Raca, Gordana; Mirkin, Sergei M. (November 1997). "Trinucleotide repeats affect DNA replication in vivo". Nature Genetics. 17 (3): 298–304. doi:10.1038/ng1197-298. ISSN 1546-1718. PMID 9354793. S2CID 6341978.
  15. ^ Krasilnikova, M M; Samadashwily, G M; Krasilnikov, A S; Mirkin, S M (1998-09-01). "Transcription through a simple DNA repeat blocks replication elongation". The EMBO Journal. 17 (17): 5095–5102. doi:10.1093/emboj/17.17.5095. ISSN 0261-4189. PMC 1170837. PMID 9724645.
  16. ^ Krasilnikova, Maria M.; Mirkin, Sergei M. (March 2004). "Replication Stalling at Friedreich's Ataxia (GAA)n Repeats In Vivo". Molecular and Cellular Biology. 24 (6): 2286–2295. doi:10.1128/MCB.24.6.2286-2295.2004. ISSN 0270-7306. PMC 355872. PMID 14993268.
  17. ^ Mirkin, Ekaterina V.; Mirkin, Sergei M. (February 2005). "Mechanisms of transcription-replication collisions in bacteria". Molecular and Cellular Biology. 25 (3): 888–895. doi:10.1128/MCB.25.3.888-895.2005. ISSN 0270-7306. PMC 544003. PMID 15657418.
  18. ^ Mirkin, Ekaterina V.; Mirkin, Sergei M. (March 2007). "Replication Fork Stalling at Natural Impediments". Microbiology and Molecular Biology Reviews. 71 (1): 13–35. doi:10.1128/MMBR.00030-06. ISSN 1092-2172. PMC 1847372. PMID 17347517.
  19. ^ Mirkin, Sergei M. (June 2007). "Expandable DNA repeats and human disease". Nature. 447 (7147): 932–940. Bibcode:2007Natur.447..932M. doi:10.1038/nature05977. ISSN 1476-4687. PMID 17581576. S2CID 4397592.
  20. ^ Voineagu, Irina; Narayanan, Vidhya; Lobachev, Kirill S.; Mirkin, Sergei M. (2008-07-22). "Replication stalling at unstable inverted repeats: Interplay between DNA hairpins and fork stabilizing proteins". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 9936–9941. Bibcode:2008PNAS..105.9936V. doi:10.1073/pnas.0804510105. ISSN 0027-8424. PMC 2481305. PMID 18632578.
  21. ^ Shishkin, Alexander A.; Voineagu, Irina; Matera, Robert; Cherng, Nicole; Chernet, Brook T.; Krasilnikova, Maria M.; Narayanan, Vidhya; Lobachev, Kirill S.; Mirkin, Sergei M. (2009-07-10). "Large-scale expansions of Friedreich's ataxia GAA repeats in yeast". Molecular Cell. 35 (1): 82–92. doi:10.1016/j.molcel.2009.06.017. ISSN 1097-4164. PMC 2722067. PMID 19595718.
  22. ^ Shah, Kartik A.; Shishkin, Alexander A.; Voineagu, Irina; Pavlov, Youri I.; Shcherbakova, Polina V.; Mirkin, Sergei M. (2012-11-29). "Role of DNA polymerases in repeat-mediated genome instability". Cell Reports. 2 (5): 1088–1095. doi:10.1016/j.celrep.2012.10.006. ISSN 2211-1247. PMC 3513503. PMID 23142667.
  23. ^ Aksenova, Anna Y.; Greenwell, Patricia W.; Dominska, Margaret; Shishkin, Alexander A.; Kim, Jane C.; Petes, Thomas D.; Mirkin, Sergei M. (2013-12-03). "Genome rearrangements caused by interstitial telomeric sequences in yeast". Proceedings of the National Academy of Sciences of the United States of America. 110 (49): 19866–19871. Bibcode:2013PNAS..11019866A. doi:10.1073/pnas.1319313110. ISSN 1091-6490. PMC 3856781. PMID 24191060.
  24. ^ Kim, Jane C.; Harris, Samantha T.; Dinter, Teresa; Shah, Kartik A.; Mirkin, Sergei M. (January 2017). "The role of break-induced replication in large-scale expansions of (CAG)n•(CTG)n repeats". Nature Structural & Molecular Biology. 24 (1): 55–60. doi:10.1038/nsmb.3334. ISSN 1545-9993. PMC 5215974. PMID 27918542.
  25. ^ Neil, Alexander J.; Liang, Miranda U.; Khristich, Alexandra N.; Shah, Kartik A.; Mirkin, Sergei M. (2018-04-20). "RNA-DNA hybrids promote the expansion of Friedreich's ataxi (GAA)n repeats via break-induced replication". Nucleic Acids Research. 46 (7): 3487–3497. doi:10.1093/nar/gky099. ISSN 1362-4962. PMC 5909440. PMID 29447396.
  26. ^ Kononenko, Artem V.; Ebersole, Thomas; Vasquez, Karen M.; Mirkin, Sergei M. (August 2018). "Mechanisms of genetic instability caused by (CGG)n repeats in an experimental mammalian system". Nature Structural & Molecular Biology. 25 (8): 669–676. doi:10.1038/s41594-018-0094-9. ISSN 1545-9985. PMC 6082162. PMID 30061600.
  27. ^ Khristich, Alexandra N.; Armenia, Jillian F.; Matera, Robert M.; Kolchinski, Anna A.; Mirkin, Sergei M. (2020-01-21). "Large-scale contractions of Friedreich's ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability". Proceedings of the National Academy of Sciences of the United States of America. 117 (3): 1628–1637. Bibcode:2020PNAS..117.1628K. doi:10.1073/pnas.1913416117. ISSN 1091-6490. PMC 6983365. PMID 31911468.
  28. ^ Neil, Alexander J.; Hisey, Julia A.; Quasem, Ishtiaque; McGinty, Ryan J.; Hitczenko, Marcin; Khristich, Alexandra N.; Mirkin, Sergei M. (2021-02-02). "Replication-independent instability of Friedreich's ataxia GAA repeats during chronological aging". Proceedings of the National Academy of Sciences of the United States of America. 118 (5): e2013080118. Bibcode:2021PNAS..11813080N. doi:10.1073/pnas.2013080118. ISSN 1091-6490. PMC 7865128. PMID 33495349.
  29. ^ Matos-Rodrigues, Gabriel; Wietmarschen, Niek van; Wu, Wei; Tripathi, Veenu; Koussa, Natasha C.; Pavani, Raphael; Nathan, William J.; Callen, Elsa; Belinky, Frida; Mohammed, Ashraf; Napierala, Marek; Usdin, Karen; Ansari, Aseem Z.; Mirkin, Sergei M.; Nussenzweig, André (2022-10-06). "S1-END-seq reveals DNA secondary structures in human cells". Molecular Cell. 82 (19): 3538–3552.e5. doi:10.1016/j.molcel.2022.08.007. ISSN 1097-2765. PMC 9547894. PMID 36075220.{{cite journal}}: CS1 maint: PMC embargo expired (link)
  30. ^ Masnovo, Chiara; Lobo, Ayesha F.; Mirkin, Sergei M. (October 2022). "Replication dependent and independent mechanisms of GAA repeat instability". DNA Repair. 118: 103385. doi:10.1016/j.dnarep.2022.103385. ISSN 1568-7856. PMC 9675320. PMID 35952488.{{cite journal}}: CS1 maint: PMC embargo expired (link)
  31. ^ L, I’m going to DNA Disney; Says, ! | Marathonsam (2014-07-18). "FASEB Summer Research Conference on Dynamic DNA Structures in Biology: Sergei Mirkin". PLOS Biologue. Retrieved 2022-11-08.
  32. ^ "2016 DNA Damage, Mutation and Cancer Conference GRC". www.grc.org. Retrieved 2022-11-08.
  33. ^ "19th Annual Midwest DNA Repair Symposium | Wright State University". www.wright.edu. Retrieved 2022-11-08.
  34. ^ "2018 Mutagenesis Conference GRC". www.grc.org. Retrieved 2022-11-08.
  35. ^ "Faculty Highlights 2019-2020 | Department of Biology". as.tufts.edu. Retrieved 2022-11-08.
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