Sergei Mirkin Explained
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.
Early life and education
Mirkin 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
Mirkin 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 Web site: 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
- 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 . 10.1038/330495a0 . 2825028 . 1987Natur.330..495M . 4360764 .
- Samadashwily . G.M. . Dayn . A. . Mirkin . S.M. . Suicidal nucleotide sequences for DNA polymerization. . The EMBO Journal . December 1993 . 12 . 13 . 4975–4983 . 10.1002/j.1460-2075.1993.tb06191.x . 8262040 . 413758 .
- Cox . Randal . Mirkin . Sergei M. . Characteristic enrichment of DNA repeats in different genomes . Proceedings of the National Academy of Sciences . 13 May 1997 . 94 . 10 . 5237–5242 . 10.1073/pnas.94.10.5237 . 7574496 . 1997PNAS...94.5237C . free . 24662 .
- Samadashwily . George M. . Raca . Gordana . Mirkin . Sergei M. . Trinucleotide repeats affect DNA replication in vivo . Nature Genetics . November 1997 . 17 . 3 . 298–304 . 10.1038/ng1197-298 . 9354793 . 6341978 .
- Krasilnikova . M. M. . Transcription through a simple DNA repeat blocks replication elongation . The EMBO Journal . 1 September 1998 . 17 . 17 . 5095–5102 . 10.1093/emboj/17.17.5095 . 1170837 . 9724645 .
- Krasilnikova . Maria M. . Mirkin . Sergei M. . Replication Stalling at Friedreich's Ataxia (GAA) n Repeats In Vivo . Molecular and Cellular Biology . 1 March 2004 . 24 . 6 . 2286–2295 . 10.1128/MCB.24.6.2286-2295.2004 . 14993268 . 355872 .
- Mirkin . Ekaterina V. . Mirkin . Sergei M. . Mechanisms of Transcription-Replication Collisions in Bacteria . Molecular and Cellular Biology . 1 February 2005 . 25 . 3 . 888–895 . 10.1128/MCB.25.3.888-895.2005 . 15657418 . 544003 .
- Mirkin . Ekaterina V. . Mirkin . Sergei M. . Replication Fork Stalling at Natural Impediments . Microbiology and Molecular Biology Reviews . March 2007 . 71 . 1 . 13–35 . 10.1128/MMBR.00030-06 . 1847372 . 17347517 .
- Mirkin . Sergei M. . Expandable DNA repeats and human disease . Nature . June 2007 . 447 . 7147 . 932–940 . 10.1038/nature05977 . 17581576 . 2007Natur.447..932M . 4397592 .
- Voineagu . Irina . Narayanan . Vidhya . Lobachev . Kirill S. . Mirkin . Sergei M. . Replication stalling at unstable inverted repeats: Interplay between DNA hairpins and fork stabilizing proteins . Proceedings of the National Academy of Sciences . 22 July 2008 . 105 . 29 . 9936–9941 . 10.1073/pnas.0804510105 . 2481305 . 18632578 . 2008PNAS..105.9936V . free .
- 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 . 10.1038/nsmb.1527 . 2837601 . 19136957 .
- Shishkin . Alexander A. . Voineagu . Irina . Matera . Robert . Cherng . Nicole . Chernet . Brook T. . Krasilnikova . Maria M. . Narayanan . Vidhya . Lobachev . Kirill S. . Mirkin . Sergei M. . Large-Scale Expansions of Friedreich's Ataxia GAA Repeats in Yeast . Molecular Cell . July 2009 . 35 . 1 . 82–92 . 10.1016/j.molcel.2009.06.017 . 2722067 . 19595718 .
- Shah . Kartik A. . Shishkin . Alexander A. . Voineagu . Irina . Pavlov . Youri I. . Shcherbakova . Polina V. . Mirkin . Sergei M. . Role of DNA Polymerases in Repeat-Mediated Genome Instability . Cell Reports . November 2012 . 2 . 5 . 1088–1095 . 10.1016/j.celrep.2012.10.006 . 3513503 . 23142667 .
- Aksenova . Anna Y. . Greenwell . Patricia W. . Dominska . Margaret . Shishkin . Alexander A. . Kim . Jane C. . Petes . Thomas D. . Mirkin . Sergei M. . Genome rearrangements caused by interstitial telomeric sequences in yeast . Proceedings of the National Academy of Sciences . 3 December 2013 . 110 . 49 . 19866–19871 . 10.1073/pnas.1319313110 . 3856781 . 24191060 . 2013PNAS..11019866A . free .
- Kim . Jane C . Harris . Samantha T . Dinter . Teresa . Shah . Kartik A . Mirkin . Sergei M . The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats . Nature Structural & Molecular Biology . January 2017 . 24 . 1 . 55–60 . 10.1038/nsmb.3334 . 5215974 . 27918542 .
- Neil . Alexander J . Liang . Miranda U . Khristich . Alexandra N . Shah . Kartik A . Mirkin . Sergei M . RNA–DNA hybrids promote the expansion of Friedreich's ataxia (GAA)n repeats via break-induced replication . Nucleic Acids Research . 20 April 2018 . 46 . 7 . 3487–3497 . 10.1093/nar/gky099 . 5909440 . 29447396 .
- Kononenko . Artem V. . Ebersole . Thomas . Vasquez . Karen M. . Mirkin . Sergei M. . Mechanisms of genetic instability caused by (CGG)n repeats in an experimental mammalian system . Nature Structural & Molecular Biology . August 2018 . 25 . 8 . 669–676 . 10.1038/s41594-018-0094-9 . 6082162 . 30061600 .
- Khristich . Alexandra N. . Armenia . Jillian F. . Matera . Robert M. . Kolchinski . Anna A. . Mirkin . Sergei M. . 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 . 21 January 2020 . 117 . 3 . 1628–1637 . 10.1073/pnas.1913416117 . 6983365 . 31911468 . 2020PNAS..117.1628K . free .
- Khristich . Alexandra N. . Mirkin . Sergei M. . March 2020. On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability . Journal of Biological Chemistry . en . 295 . 13 . 4134–4170 . 10.1074/jbc.REV119.007678 . free . 7105313 . 32060097.
- Neil . Alexander J. . Hisey . Julia A. . Quasem . Ishtiaque . McGinty . Ryan J. . Hitczenko . Marcin . Khristich . Alexandra N. . Mirkin . Sergei M. . Replication-independent instability of Friedreich's ataxia GAA repeats during chronological aging . Proceedings of the National Academy of Sciences . 2 February 2021 . 118 . 5 . 10.1073/pnas.2013080118 . 7865128 . 33495349 . 2021PNAS..11813080N . free .
- 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 . S1-END-seq reveals DNA secondary structures in human cells . Molecular Cell . October 2022 . 82 . 19 . 3538–3552.e5 . 10.1016/j.molcel.2022.08.007 . 36075220 . 9547894 .
- Rastokina . A . Cebrián . J . Mozafari . N . Mandel . NH . Smith . CIE . Lopes . M . Zain . R . Mirkin . SM . 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 . 8 September 2023 . 51 . 16 . 8532–8549 . 10.1093/nar/gkad441 . 37216608. 10484681 .
- Matos-Rodrigues . G . Hisey . JA . Nussenzweig . A . Mirkin . SM . Detection of alternative DNA structures and its implications for human disease. . Molecular Cell . 19 October 2023 . 83 . 20 . 3622–3641 . 10.1016/j.molcel.2023.08.018 . 37863029.
- Hisey . JA . Radchenko . EA . Mandel . NH . McGinty . RJ . Matos-Rodrigues . G . Rastokina . A . Masnovo . C . Ceschi . S . Hernandez . A . Nussenzweig . A . Mirkin . SM . Pathogenic CANVAS (AAGGG)n repeats stall DNA replication due to the formation of alternative DNA structures. . Nucleic Acids Research . 21 February 2024 . 10.1093/nar/gkae124 . 38381906. free . 11077069 .
Awards and honors
- Editor-in-Chief, Current Opinions in Genetics and Development, 2010-2013
- Distinguished Senior Scholar Award, Tufts University, 2020
Notes and References
- Mirkin . S. M. . Thinking of R.B. Khesin . Molecular Biology . 2002 . 36 . 2 . 267–279 . . 10.1023/A:1015334325856 . 1820228 .
- Book: Soyfer . Valery N. . Potaman . Vladimir N. . Triple-Helical Nucleic Acids . 1996 . 10.1007/978-1-4612-3972-7 . 978-1-4612-8454-3 . 2354265 . en.
- News: Lane . Earl . Soviet Science Hits the Road . Newspapers.com . Newsday . December 1991 . en.
- News: Helix heresy . New Scientist.
- Katsnelson . Alla . Genome punctuation . The Journal of Cell Biology . 5 June 2006 . 173 . 5 . 643a . 10.1083/jcb.1735rr3.
- Genetics: DNA potholes . Nature . 24 July 2008 . 454 . 7203 . 371–371 . 10.1038/454371f.