Kim Nasmyth

Last updated

Kim Nasmyth
FRS FMedSci
KimNasmyth.jpg
Nasmyth in 2017
Born
Kim Ashley Nasmyth

(1952-10-10) 10 October 1952 (age 71) [1]
NationalityBritish [2]
Education Eton College
Alma mater
Known for Cohesin
Spouse
Anna Dowson
​
(m. 1982)​
[1]
ChildrenTwo [1]
Awards
Scientific career
Fieldsmolecular biology, gene regulation, cell cycle control
Institutions
Thesis DNA replication in Schizosaccharomyces pombe  (1977)
Doctoral advisor Murdoch Mitchison [4] [5]
Notable students
Website www.bioch.ox.ac.uk/research/nasmyth

Kim Ashley Nasmyth (born 18 October 1952) [1] is an English geneticist, the Whitley Professor of Biochemistry at the University of Oxford, a Fellow of Trinity College, Oxford, former scientific director of the Research Institute of Molecular Pathology (IMP), and former head of the Department of Biochemistry, University of Oxford. [6] [7] He is best known for his work on the segregation of chromosomes during cell division.

Contents

Early life and education

Nasmyth was born in London in 1952 of James Ashley (Jan) Nasmyth and Jenny Hughes. [1] [8] His father Jan was doubly descended from King Charles II and founder of the billion dollar publishing company Argus Media. [8] [9] He attended Eton College, Berkshire, then the University of York, where he studied Biology. [1] Nasmyth went on to complete his graduate studies in the group of Murdoch Mitchison at the University of Edinburgh. Here he worked on the cell cycle alongside Paul Nurse [5] and his PhD thesis focused on the control of DNA replication in fission yeast. [4] In Mitchison's lab he made substantial contributions to the study of the cell cycle in fission yeast isolating and characterising cell cycle mutants and the first identification of a gene product (DNA ligase) in these mutants. [10]

Career and research

Kim Nasmyth explaining loop extrusion with a climbing rope Prof Kim Nasmyth explains loop extrusion with climbing rope.jpg
Kim Nasmyth explaining loop extrusion with a climbing rope
The cohesin complex entrapping sister DNAs Cohesin Holocomplex.png
The cohesin complex entrapping sister DNAs

Nasmyth joined Ben Hall's lab in Seattle as a postdoctoral researcher where he developed ways of cloning genes by complementation in yeast and, in collaboration with Steve Reed, cloned the CDC28 gene from the budding yeast Saccharomyces cerevisiae . [5]

As a group leader in Cambridge Nasmyth became interested in the phenomenon of mating-type switching in yeast. Together with Kelly Tatchell he cloned the S. cerevisiae mating-type locus and found, surprisingly, that 'silent' copies of the mating-type genes including their promoters are maintained in the yeast chromosome. This represented the first case where the position of a gene in the chromosome had demonstrable biological significance, and prompted Nasmyth to abandon work on the cell cycle for a time and concentrate instead on studying gene silencing. [5] He was one of the first to demonstrate that gene expression can be regulated through specific control elements which are distant from the start of transcription. [10]

Max Birnstiel invited Nasmyth to join him at the then newly founded Research Institute of Molecular Pathology (IMP) in Vienna, Austria, where he was director. Nasmyth became one of the first three senior group leaders that Birnstiel recruited in 1986. [11] At the IMP, Nasmyth changed his focus from gene silencing back to cell cycle control. In the mid-1990s Nasmyth co-discovered the APC/C and showed that its activity induces chromosome segregation. [12] Using temperature-sensitive mutants of the APC/C he found several genes which are required for sister chromatid cohesion [13] which we now know encode subunits of the cohesin complex. Nasmyth has since shown that cohesin forms a ring, [14] that sister chromatids are held together within this ring [15] and that they are released by cleavage of cohesin by separase. [16] Following Max Birnstiel's retirement, Nasmyth became scientific director of the IMP in 1997. [17]

In 2006, Nasmyth left the IMP to become head of the Department of Biochemistry of the University of Oxford, a post he held until 2011. Nasmyth continues to head a research group at this department. He is a member of the Advisory Council for the Campaign for Science and Engineering. [18] [19] [20] His research has been funded by the Medical Research Council (MRC), the Wellcome Trust, and Cancer Research UK. [21] [22] [23] [24] He plans to retire from research in 2022. [23]

Awards and honours

Nasmyth has also been awarded the following:

Personal life

Nasmyth married Anna Dowson, daughter of Sir Philip Dowson, in 1982 [31] and has two daughters. [1] His younger brother is furniture designer, Luke Hughes. [32] He enjoys skiing and climbing, [6] a hobby to which he attributes his theory of how cohesin works. [33] [34] He also co-owns a vineyard in the south of France. [35] Nasmyth held a large number of shares in his fathers billion dollar company Argus Media until its purchase by General Atlantic in 2016. [36] [37] In 2014 he was appointed director of Badger Lane Management company. [2] During his time in Vienna, Nasmyth became Austrian citizen. [38]

Related Research Articles

<span class="mw-page-title-main">Condensin</span> Protein complex

Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis. Their subunits were originally identified as major components of mitotic chromosomes assembled in Xenopus egg extracts.

<span class="mw-page-title-main">Spindle checkpoint</span> Cell cycle checkpoint

The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.

<span class="mw-page-title-main">Kinetochore</span> Protein complex that allows microtubules to attach to chromosomes during cell division

A kinetochore is a disc-shaped protein structure associated with duplicated chromatids in eukaryotic cells where the spindle fibers attach during cell division to pull sister chromatids apart. The kinetochore assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. The term kinetochore was first used in a footnote in a 1934 Cytology book by Lester W. Sharp and commonly accepted in 1936. Sharp's footnote reads: "The convenient term kinetochore has been suggested to the author by J. A. Moore", likely referring to John Alexander Moore who had joined Columbia University as a freshman in 1932.

<span class="mw-page-title-main">Separase</span> Mammalian protein found in Homo sapiens

Separase, also known as separin, is a cysteine protease responsible for triggering anaphase by hydrolysing cohesin, which is the protein responsible for binding sister chromatids during the early stage of anaphase. In humans, separin is encoded by the ESPL1 gene.

SMC complexes represent a large family of ATPases that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

<span class="mw-page-title-main">Cohesin</span> Protein complex that regulates the separation of sister chromatids during cell division

Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3. Cohesin holds sister chromatids together after DNA replication until anaphase when removal of cohesin leads to separation of sister chromatids. The complex forms a ring-like structure and it is believed that sister chromatids are held together by entrapment inside the cohesin ring. Cohesin is a member of the SMC family of protein complexes which includes Condensin, MukBEF and SMC-ScpAB.

Mad2 is an essential spindle checkpoint protein. The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. The Mad2 gene was first identified in the yeast S. cerevisiae in a screen for genes which when mutated would confer sensitivity to microtubule poisons. The human orthologues of Mad2 were first cloned in a search for human cDNAs that would rescue the microtubule poison-sensitivity of a yeast strain in which a kinetochore binding protein was missing. The protein was shown to be present at unattached kinetochores and antibody inhibition studies demonstrated it was essential to execute a block in the metaphase-to-anaphase transition in response to the microtubule poison nocodazole. Subsequent cloning of the Xenopus laevis orthologue, facilitated by the sharing of the human sequence, allowed for the characterization of the mitotic checkpoint in egg extracts.

Anaphase lag is a consequence of an event during cell division where sister chromatids do not properly separate from each other because of improper spindle formation. The chromosome or chromatid does not properly migrate during anaphase and the daughter cells will lose some genetic information. It is one of many causes of aneuploidy. This event can occur during both meiosis and mitosis with unique repercussions. In either case, anaphase lag will cause one daughter cell to receive a complete set of chromosomes while the other lacks one paired set of chromosomes, creating a form of monosomy. Whether the cell survives depends on which sister chromatid was lost and the background genomic state of the cell. The passage of abnormal numbers of chromosomes will have unique consequences with regards to mosaicism and development as well as the progression and heterogeneity of cancers.

Chromosome segregation is the process in eukaryotes by which two sister chromatids formed as a consequence of DNA replication, or paired homologous chromosomes, separate from each other and migrate to opposite poles of the nucleus. This segregation process occurs during both mitosis and meiosis. Chromosome segregation also occurs in prokaryotes. However, in contrast to eukaryotic chromosome segregation, replication and segregation are not temporally separated. Instead segregation occurs progressively following replication.

<span class="mw-page-title-main">RAD21</span> Protein-coding gene in humans

Double-strand-break repair protein rad21 homolog is a protein that in humans is encoded by the RAD21 gene. RAD21, an essential gene, encodes a DNA double-strand break (DSB) repair protein that is evolutionarily conserved in all eukaryotes from budding yeast to humans. RAD21 protein is a structural component of the highly conserved cohesin complex consisting of RAD21, SMC1A, SMC3, and SCC3 [ STAG1 (SA1) and STAG2 (SA2) in multicellular organisms] proteins, involved in sister chromatid cohesion.

<span class="mw-page-title-main">WAPAL</span> Protein-coding gene in the species Homo sapiens

Wings apart-like protein homolog (WAPL) is a protein that in humans is encoded by the WAPAL gene. WAPL is a key regulator of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2. Cohesin has a ring-like arrangement and it is thought that it associates with the chromosome by entrapping it whether as a loop of DNA, a single strand or a pair of sister chromosomes. WAPL forms a complex with PDS5A or PDS5B and releases cohesin from DNA by opening the interface between SMC3 and RAD21.

<span class="mw-page-title-main">Shugoshin 1</span> Protein-coding gene in the species Homo sapiens

Shugoshin 1 or Shugoshin-like 1, is a protein that in humans is encoded by the SGO1 gene.

<span class="mw-page-title-main">REC8</span> Protein-coding gene in the species Homo sapiens

Meiotic recombination protein REC8 homolog is a protein that in humans is encoded by the REC8 gene.

G1/S-specific cyclin Cln3 is a protein that is encoded by the CLN3 gene. The Cln3 protein is a budding yeast G1 cyclin that controls the timing of Start, the point of commitment to a mitotic cell cycle. It is an upstream regulator of the other G1 cyclins, and it is thought to be the key regulator linking cell growth to cell cycle progression. It is a 65 kD, unstable protein; like other cyclins, it functions by binding and activating cyclin-dependent kinase (CDK).

<span class="mw-page-title-main">Research Institute of Molecular Pathology</span>

The Research Institute of Molecular Pathology (IMP) is a biomedical research center, which conducts curiosity-driven basic research in the molecular life sciences.

<span class="mw-page-title-main">Angelika Amon</span> Austrian American academic molecular and cell biologist (1967–2020)

Angelika Amon was an Austrian American molecular and cell biologist, and the Kathleen and Curtis Marble Professor in Cancer Research at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, United States. Amon's research centered on how chromosomes are regulated, duplicated, and partitioned in the cell cycle. Amon was elected to the American Academy of Arts and Sciences in 2017.

Sister chromatid cohesion refers to the process by which sister chromatids are paired and held together during certain phases of the cell cycle. Establishment of sister chromatid cohesion is the process by which chromatin-associated cohesin protein becomes competent to physically bind together the sister chromatids. In general, cohesion is established during S phase as DNA is replicated, and is lost when chromosomes segregate during mitosis and meiosis. Some studies have suggested that cohesion aids in aligning the kinetochores during mitosis by forcing the kinetochores to face opposite cell poles.

<span class="mw-page-title-main">SMC1B</span> Protein-coding gene in the species Homo sapiens

Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the SMC1B gene. SMC proteins engage in chromosome organization and can be broken into 3 groups based on function which are cohesins, condensins, and DNA repair. SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1B protein appears to participate with other cohesins REC8, STAG3 and SMC3 in sister-chromatid cohesion throughout the whole meiotic process in human oocytes.

<span class="mw-page-title-main">Frank Uhlmann</span>

Frank Uhlmann FRS is a group leader at the Francis Crick Institute in London.

Xenopus egg extract is a lysate that is prepared by crushing the eggs of the African clawed frog Xenopus laevis. It offers a powerful cell-free system for studying various cell biological processes, including cell cycle progression, nuclear transport, DNA replication and chromosome segregation. It is also called Xenopus egg cell-free system or Xenopus egg cell-free extract.

References

  1. 1 2 3 4 5 6 7 Anon (2016). "Nasmyth, Prof. Kim Ashley" . Who's Who (online Oxford University Press  ed.). A & C Black. doi:10.1093/ww/9780199540884.013.29204.(Subscription or UK public library membership required.)
  2. 1 2 "Kim NASMYTH - Personal Appointments (free information from Companies House)". beta.companieshouse.gov.uk. Retrieved 5 December 2017.
  3. ↑ Louis-Jeantet Prize
  4. 1 2 Nasmyth, Kim (1977). DNA replication in Schizosaccharomyces pombe (PhD thesis). University of Edinburgh. hdl:1842/15490. OCLC   606123690. EThOS   uk.bl.ethos.659887. Lock-green.svg
  5. 1 2 3 4 Tebb, Graham (1998). "Kim Nasmyth: the universal truth". Current Biology. 8 (8): R257–R258. doi: 10.1016/S0960-9822(98)70165-4 . PMID   9550707.
  6. 1 2 Anon (2004). "Movers: Kim Nasmyth, Whitley chair of biochemistry, University of Oxford, UK". Nature. 428 (6980): 350. doi: 10.1038/nj6980-350c .
  7. ↑ Schwob, E; Böhm, T; Mendenhall, M. D.; Nasmyth, K (1994). "The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. Cerevisiae". Cell. 79 (2): 233–44. doi:10.1016/0092-8674(94)90193-7. PMID   7954792. S2CID   34939988.
  8. 1 2 "Jan Nasmyth". Daily Telegraph. 15 October 2008. ISSN   0307-1235 . Retrieved 5 December 2017.
  9. ↑ "James Ashley (Jan) Nasmyth (1918-2008)". groups.google.com. Retrieved 5 December 2017.
  10. 1 2 "DServe Archive Catalog Show". collections.royalsociety.org. Retrieved 4 March 2016.
  11. ↑ "History of the IMP" . Retrieved 29 November 2017.
  12. ↑ Irniger, S.; Piatti, S.; Michaelis, C.; Nasmyth, K. (21 April 1995). "Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast". Cell. 81 (2): 269–278. doi: 10.1016/0092-8674(95)90337-2 . ISSN   0092-8674. PMID   7736579. S2CID   15424287.
  13. ↑ Michaelis, C.; Ciosk, R.; Nasmyth, K. (3 October 1997). "Cohesins: chromosomal proteins that prevent premature separation of sister chromatids". Cell. 91 (1): 35–45. doi: 10.1016/s0092-8674(01)80007-6 . ISSN   0092-8674. PMID   9335333. S2CID   18572651.
  14. ↑ Gruber, Stephan; Haering, Christian H.; Nasmyth, Kim (21 March 2003). "Chromosomal cohesin forms a ring". Cell. 112 (6): 765–777. doi: 10.1016/s0092-8674(03)00162-4 . ISSN   0092-8674. PMID   12654244. S2CID   15563936.
  15. ↑ Gligoris, Thomas G.; Scheinost, Johanna C.; Bürmann, Frank; Petela, Naomi; Chan, Kok-Lung; Uluocak, Pelin; Beckouët, Frédéric; Gruber, Stephan; Nasmyth, Kim (21 November 2014). "Closing the cohesin ring: structure and function of its Smc3-kleisin interface". Science. 346 (6212): 963–967. Bibcode:2014Sci...346..963G. doi:10.1126/science.1256917. ISSN   1095-9203. PMC   4300515 . PMID   25414305.
  16. ↑ Uhlmann, F.; Wernic, D.; Poupart, M. A.; Koonin, E. V.; Nasmyth, K. (27 October 2000). "Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast". Cell. 103 (3): 375–386. doi: 10.1016/s0092-8674(00)00130-6 . ISSN   0092-8674. PMID   11081625. S2CID   2667617.
  17. ↑ "IMP Management" . Retrieved 29 November 2017.
  18. ↑ "Advisory Council of the Campaign for Science and Engineering". Archived from the original on 28 August 2010. Retrieved 11 February 2011.
  19. ↑ Tóth, A; Ciosk, R; Uhlmann, F; Galova, M; Schleiffer, A; Nasmyth, K (1999). "Yeast cohesin complex requires a conserved protein, Eco1p(Ctf7), to establish cohesion between sister chromatids during DNA replication". Genes & Development. 13 (3): 320–33. doi:10.1101/gad.13.3.320. PMC   316435 . PMID   9990856.
  20. ↑ Nasmyth, K; Peters, J. M.; Uhlmann, F (2000). "Splitting the chromosome: Cutting the ties that bind sister chromatids". Science. 288 (5470). New York, N.Y.: 1379–85. Bibcode:2000Sci...288.1379N. doi:10.1126/science.288.5470.1379. PMID   10827941.
  21. ↑ "UK Government research grants awarded to Kim Nasmyth". Swindon: Research Councils UK. Archived from the original on 3 June 2015.
  22. ↑ "Kim Nasmyth : Cancer Research UK". 15 November 2015. Archived from the original on 15 November 2015. Retrieved 5 December 2017.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  23. 1 2 Oneltd (17 November 2015). "Trinity College – Professorial Fellow wins Wellcome Trust award". trinity.ox.ac.uk. Retrieved 5 December 2017.
  24. ↑ "Lord of the Rings – Cohesin and cancer". Cancer Research UK - Science blog. Retrieved 5 December 2017.
  25. ↑ "Professor Kim Nasmyth FMedSci FRS". London: Royal Society. Archived from the original on 17 November 2015.
  26. 1 2 3 4 5 6 "Keynote Lectures Detailed Information".
  27. ↑ de médecine 1997 and Travaux de recherche Archived 30 January 2016 at the Wayback Machine
  28. ↑ Wittgensteinpreis-Träger 1999 Univ. Prof. Dr. Kim Ashley Nasmyth Archived 8 June 2015 at the Wayback Machine
  29. ↑ "Professor Kim Nasmyth | the Academy of Medical Sciences".
  30. ↑ Breakthrough Prize in Life Sciences 2018
  31. ↑ "CSHL Archives Repository | Invitation to the marriage of Kim Nasmyth and Anna Dowson". libgallery.cshl.edu. 1982. Retrieved 4 December 2017.
  32. ↑ Walker, Aidan (2020). Furniture in Architecture. Thames & Hudson. p. 14. ISBN   9780500022542.
  33. ↑ "These 12 People Are Changing Science". Time. Retrieved 5 December 2017.
  34. ↑ Breakthrough (3 December 2017), LIVE - Morgan Freeman hosts the Breakthrough Prize | Nat Geo Live , retrieved 4 December 2017
  35. ↑ "Le Mazelet | Le Mazelet". lemazelet.com. Retrieved 5 December 2017.
  36. ↑ Williams, Christopher (2016). "Family owners of Argus Media in line for £500m payout from sale". Daily Telegraph. ISSN   0307-1235 . Retrieved 5 December 2017.
  37. ↑ "ARGUS MEDIA LIMITED - Annual return made up to 7 June 2016 with full list of shareholders". beta.companieshouse.gov.uk. Retrieved 5 December 2017.
  38. ↑ "DerStandard.at".
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