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Sergei Mirkin (born September 29, 1956) is a Russian-American biologist who studies genome instability mediated by repetitive DNA during DNA replication and transcription. He is a professor of Genetics and Molecular Biology and holds the White Family Chair in Biology at Tufts University.
Sergei Mirkin | |
---|---|
Born | September 29, 1956 Moscow, Russia |
Alma mater | Moscow State University, Russian Academy of Sciences |
Known for | Genome instability |
Scientific career | |
Fields | Biology, genomics |
Institutions | Tufts University |
Early life and education
editMirkin was born in Moscow, Russia. He attended Moscow State University, where he earned both a Bachelor of Science and a Master of Science degree in Genetics in 1978. Mirkin went on to pursue a PhD in Molecular Biology at the Russian Academy of Sciences’ Institute of Molecular Genetics. His PhD was under the supervision of Roman B. Khesin, a molecular biologist and Mirkin later described his formative years in the Khesin lab in his essay, “Thinking of R.B. Khesin”.[1] By studying conditionally lethal mutants of DNA gyrase, he established a fundamental interplay between DNA supercoiling and transcription in E. coli.
Career and research
editMirkin conducted his postdoctoral studies at the Institute of Molecular Genetics with Maxim Frank-Kamenetskii, a biophysicist. This work culminated with the discovery of the three-stranded H-DNA structure.[2] Mirkin moved to the US as a Fogarty International Fellow in 1989 and joined the faculty of the Department of Genetics at University of Illinois Chicago (UIC) in 1990.[3] 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.
Mirkin’s major contributions to science include discovering of the first multi-stranded DNA structure (H-DNA); detection of dynamic non-B DNA structures, including DNA cruciforms and triplexes in vivo; discovery that replication through trinucleotide repeats is compromised due to their unusual structures[4] resulting in trinucleotide repeat disorder and unraveling the mechanisms and consequences of transcription-replication collisions in vivo.[5] [6]
The "Mirkin Lab". continues studying genome structure and function from two perspectives: the mechanisms responsible for the instability of DNA repeats implicated in human disease, the role of transcription-replication collisions in genome instability and the mechanisms of genome instability mediated at interstitial telomeric sequences.
Selected publications
edit- 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. PMID 2825028. S2CID 4360764.
- Samadashwily, G.M.; Dayn, A.; Mirkin, S.M. (December 1993). "Suicidal nucleotide sequences for DNA polymerization". The EMBO Journal. 12 (13): 4975–4983. doi:10.1002/j.1460-2075.1993.tb06191.x. PMC 413758. PMID 8262040.
- Cox, Randal; Mirkin, Sergei M. (13 May 1997). "Characteristic enrichment of DNA repeats in different genomes". Proceedings of the National Academy of Sciences. 94 (10): 5237–5242. Bibcode:1997PNAS...94.5237C. doi:10.1073/pnas.94.10.5237. PMC 24662. PMID 7574496.
- 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. PMID 9354793. S2CID 6341978.
- Krasilnikova, M. M. (1 September 1998). "Transcription through a simple DNA repeat blocks replication elongation". The EMBO Journal. 17 (17): 5095–5102. doi:10.1093/emboj/17.17.5095. PMC 1170837. PMID 9724645.
- Krasilnikova, Maria M.; Mirkin, Sergei M. (1 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. PMC 355872. PMID 14993268.
- Mirkin, Ekaterina V.; Mirkin, Sergei M. (1 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. PMC 544003. PMID 15657418.
- 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. PMC 1847372. PMID 17347517.
- Mirkin, Sergei M. (June 2007). "Expandable DNA repeats and human disease". Nature. 447 (7147): 932–940. Bibcode:2007Natur.447..932M. doi:10.1038/nature05977. PMID 17581576. S2CID 4397592.
- Voineagu, Irina; Narayanan, Vidhya; Lobachev, Kirill S.; Mirkin, Sergei M. (22 July 2008). "Replication stalling at unstable inverted repeats: Interplay between DNA hairpins and fork stabilizing proteins". Proceedings of the National Academy of Sciences. 105 (29): 9936–9941. Bibcode:2008PNAS..105.9936V. doi:10.1073/pnas.0804510105. PMC 2481305. PMID 18632578.
- 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. PMC 2837601. PMID 19136957.
- Shishkin, Alexander A.; Voineagu, Irina; Matera, Robert; Cherng, Nicole; Chernet, Brook T.; Krasilnikova, Maria M.; Narayanan, Vidhya; Lobachev, Kirill S.; Mirkin, Sergei M. (July 2009). "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. PMC 2722067. PMID 19595718.
- Shah, Kartik A.; Shishkin, Alexander A.; Voineagu, Irina; Pavlov, Youri I.; Shcherbakova, Polina V.; Mirkin, Sergei M. (November 2012). "Role of DNA Polymerases in Repeat-Mediated Genome Instability". Cell Reports. 2 (5): 1088–1095. doi:10.1016/j.celrep.2012.10.006. PMC 3513503. PMID 23142667.
- Aksenova, Anna Y.; Greenwell, Patricia W.; Dominska, Margaret; Shishkin, Alexander A.; Kim, Jane C.; Petes, Thomas D.; Mirkin, Sergei M. (3 December 2013). "Genome rearrangements caused by interstitial telomeric sequences in yeast". Proceedings of the National Academy of Sciences. 110 (49): 19866–19871. Bibcode:2013PNAS..11019866A. doi:10.1073/pnas.1319313110. PMC 3856781. PMID 24191060.
- 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. PMC 5215974. PMID 27918542.
- Neil, Alexander J; Liang, Miranda U; Khristich, Alexandra N; Shah, Kartik A; Mirkin, Sergei M (20 April 2018). "RNA–DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication". Nucleic Acids Research. 46 (7): 3487–3497. doi:10.1093/nar/gky099. PMC 5909440. PMID 29447396.
- 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. PMC 6082162. PMID 30061600.
- Khristich, Alexandra N.; Armenia, Jillian F.; Matera, Robert M.; Kolchinski, Anna A.; Mirkin, Sergei M. (21 January 2020). "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. 117 (3): 1628–1637. Bibcode:2020PNAS..117.1628K. doi:10.1073/pnas.1913416117. PMC 6983365. PMID 31911468.
- Khristich, Alexandra N.; Mirkin, Sergei M. (March 2020). "On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability". Journal of Biological Chemistry. 295 (13): 4134–4170. doi:10.1074/jbc.REV119.007678. PMC 7105313. PMID 32060097.
- Neil, Alexander J.; Hisey, Julia A.; Quasem, Ishtiaque; McGinty, Ryan J.; Hitczenko, Marcin; Khristich, Alexandra N.; Mirkin, Sergei M. (2 February 2021). "Replication-independent instability of Friedreich's ataxia GAA repeats during chronological aging". Proceedings of the National Academy of Sciences. 118 (5). Bibcode:2021PNAS..11813080N. doi:10.1073/pnas.2013080118. PMC 7865128. PMID 33495349.
- Matos-Rodrigues, Gabriel; van Wietmarschen, Niek; 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 (October 2022). "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. PMC 9547894. PMID 36075220.
- Rastokina, A; Cebrián, J; Mozafari, N; Mandel, NH; Smith, CIE; Lopes, M; Zain, R; Mirkin, SM (8 September 2023). "Large-scale expansions of Friedreich's ataxia GAA•TTC repeats in an experimental human system: role of DNA replication and prevention by LNA-DNA oligonucleotides and PNA oligomers". Nucleic Acids Research. 51 (16): 8532–8549. doi:10.1093/nar/gkad441. PMC 10484681. PMID 37216608.
- Matos-Rodrigues, G; Hisey, JA; Nussenzweig, A; Mirkin, SM (19 October 2023). "Detection of alternative DNA structures and its implications for human disease". Molecular Cell. 83 (20): 3622–3641. doi:10.1016/j.molcel.2023.08.018. PMID 37863029.
- Hisey, JA; Radchenko, EA; Mandel, NH; McGinty, RJ; Matos-Rodrigues, G; Rastokina, A; Masnovo, C; Ceschi, S; Hernandez, A; Nussenzweig, A; Mirkin, SM (21 February 2024). "Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures". Nucleic Acids Research. doi:10.1093/nar/gkae124. PMC 11077069. PMID 38381906.
Awards and honors
edit- Editor-in-Chief, Current Opinions in Genetics and Development, 2010-2013
- Distinguished Senior Scholar Award, Tufts University, 2020
References
edit- ^ Mirkin, S. M. (2002). "Thinking of R.B. Khesin". Molecular Biology. 36 (2): 267–279. doi:10.1023/A:1015334325856. S2CID 1820228. ProQuest 760104752.[non-primary source needed]
- ^ Soyfer, Valery N.; Potaman, Vladimir N. (1996). Triple-Helical Nucleic Acids. doi:10.1007/978-1-4612-3972-7. ISBN 978-1-4612-8454-3. S2CID 2354265.
- ^ Lane, Earl (December 1991). "Soviet Science Hits the Road". Newspapers.com. Newsday.
- ^ "Helix heresy". New Scientist.
- ^ Katsnelson, Alla (5 June 2006). "Genome punctuation". The Journal of Cell Biology. 173 (5): 643a. doi:10.1083/jcb.1735rr3.
- ^ "Genetics: DNA potholes". Nature. 454 (7203): 371–371. 24 July 2008. doi:10.1038/454371f.