Kemian Nobelin palkinnonsaaja Tomas Lindahl : Alkyloidun DNA:n korjausmekanismista . T Lindal konferenssi

Emeritusprofessori   Tomas Lindal
Tomas Lindahl, svensk medborgare. Ruotsin kansalainen
 Född 1938 (77 år) i Stockholm,  Sverige Syntynyt 1938 Tukholmassa., nyt 77 vuotias.
 Disputerad 1967 vid Karolinska Institutet, Stockholm, Sverige. 
Väitellyt tohtoriksi 1967 Karoliinisessa Instituutissa.
 Professor i medicinsk och fysiologisk kemi vid Göteborgs universitet 1978–82.
 Vuosina 1978- 1982 Göteborgin Yliopiston  lääketieteellisen  ja fysiologisen kemian professori
 Emeritus group leader vid Francis Crick Institute och Emeritus director of Cancer Research UK vid Clare Hall Laboratory, Hertfordshire, Storbritannien.
Emeritus ryhmän johtaja Francis Crick-instituutissa ja Emeritus johtaja  Britannian syöpätutkimuksessa Clare Hall lboratoriossa, Hertfordshiressä.  

http://www.jbc.org/content/255/22/10569.long
Minkälaisia tutkimustöitä löydän  netistä Emeritusprofessori  Tomas Lindahlilta?  Tämän allaolevan linkin löysin M. Olssonin Facebook artikkelista.

Alkyloidun DNA:n korjaantuminen E. Colissa. O6-metyyliguaniinista siirtyy metyyliryhmä proteiinin cysteiiniin. 

Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue.

1. M Olsson and
2. T Lindahl

Tiivistelmästa suomennosta   (Abstract)

• Alkyloidusta DNA.sta näyttää 06-meG- tähteet katoavan  E.Colissa indusoidussa DNA:n  korjaussysteemissä.  Tätä reaktiota voi tutkia tarkemmin soluttomassa miljöössä käyttämällä radioaktiivisella metyloivalla agenssilla käsiteltyä DNA:ta substraattina. O6-meGg-katoamaa DNA:sta  ei seuraa radioaktiivisen materiaalin vapautuminen happoliukoisessa muodossa. Sen sijaan O6-MeG:n metyyliryhmä  näyttää siirtyneen entsymaattisesti proteiinin  Cys-aminohappoon. On havaittu radioaktiivisesti merkkautunutta S-metyylicysteiiniä proteiinihydrolysaateissa alkyloitua  DNA:ta inkuboitaessa. osittain puhdistetun E-Coli- metyylitransferaasin kanssa. Radioaktiivinen  aminohappotähde  osoittautuu identtiseksi  S-metyylicysteiinin kanssa.jos se oksidoidaan vetyperoksidilla, tulee S-metyyli cysteiinisulfonia

O6-Methylguanine residues disappear from alkylated DNA by an inducible repair process in Escherichia coli. The reaction can be studied in a cell-free system, using DNA treated with a radioactive methylating agent as substrate. The disappearance of labeled O6-methylguanine from DNA is not accompanied by release of radioactive material in an acid-soluble form. Instead, the methyl group of O6-methylguanine appears to be transferred enzymatically to a protein cysteine residue. Radioactively labeled S-methylcysteine has been identified in protein hydrolysates after incubation of the alkylated DNA with a partly purified E. coli methyltransferase activity. The radioactive amino acid residue shows properties identical with those of S-methylcysteine by automatic amino acid analysis and paper chromatography in several solvent systems. Moreover, oxidation of the compound with hydrogen peroxide yields a product which co-chromatographs with S-methylcysteine sulfone.

Tomas Lindahl Konferenssi DNA-korjausmekanismeista 

 http://dna.uio.no/lindahl/index.html
Konferenssin ohjelma on DNA- korjausmekanismiasioitten  pulssin tunnustelua:

 Tieteellinen aihe (suomennosta)  Scientific subject

• Tomas Lindal on tehnyt DNA:n korjaantumisen tutkimusalalla monta tieteen virstanpylvästä: tämän konferenssin tieteellisenä keskiönä on DNA:n korjantumisen perusasiat. Useimmat  mutageenit ja karsinogeenit aiheuttavat DNA- rakenteen   kovalentteja muutoksia. Niinpä elävä organismi on kehittänyt suuren joukon geenifunktioita, joiden spesifisenä tehtävänä on korjata tai sietää sellaisia muuntumisia elinkykyisyyden vioittumatta tai taudin kehittymättä. DNA:n korjaantumisen tärkeys normaalille olemassaololle on  todettu monesta  seikasta: On havaittu DNA:n  transkription ja DNA:n korjaantumisen välinen kytkeytyminen. On todettu  assosiaatio DNA:n korjaamisen   ja solusyklin  tarkistuskohtien (chekpoints) kesken.  On tunnistettu  ne geenit, jotka koodaavat nukleotidin (nt)  irrottamista (NER)  DNA-rihmasta  ja  huonosti pariutuvien  nukleotidien korjausmekanismia (MMR)   ja havaittu niiden olevan ihmiselle välttämättömiä  syövän ja neurologisen taudin estämiseksi. Viisikymmentä vuotta sitten tehtiin uutislöytöjä DNA:n korjaantumisesta ja niistä ajoista meidän päiviimme  DNA:n korjaantuminen  käsittää  tieteelliselle yhdyskunnalle moninaisia ja kehityksellisiä näkökohtia  suuresti merkityksellisessä  laajassa  tieteellisessä alueessa.

Tomas Lindahl made many landmark discoveries in DNA repair. The scientific focus will be on the basics of DNA repair. Most mutagenic and carcinogenic agents induce covalent changes in the structure of the DNA and living organisms have evolved a large number of gene functions specifically designed to repair or tolerate such alterations without loss of viability or development of disease. The importance of DNA repair for normal life existence has been verified by discoveries of coupling between transcription and repair, by association between DNA repair and cell- cycle checkpoints, and by identification of nucleotide excision and mismatch repair genes being essential for prevention of cancer and neurological disease in man. From the novel discoveries on DNA repair more than 5 decades ago, DNA repair today comprise diverse and evolving aspects of a broad scientific area of major significance to the scientific community.

Lindahl T. (2013) My Journey to DNA Repair. Genomics, Proteomics & Bioinformatics. 11(1):2-7. doi: 10.1016/j.gpb.2012.12.001

Programme 

(Kommenttini 13.10.2015 : Ohjelma antaa viitettä DNA:n  korjaantumista koskevan tieteen  nykyisistä keskiöistä ).

Wednesday, June 17th 2015
13:00	Lunch
13:00	Registration opens
Session I: RNA Metabolism et al
	Chair: Arne Klungland
15:00	Arne Klungland, Magnar Bjørås, Yungui Yang
	Welcome and introduction to session I
15:10	Mutsuo Sekiguchi
	Molecular tactics to escape treat of oxidative RNA damage
15:35	Nima Mosammaparast
	Ubiquitin-dependent mechanisms of alkylation repair regulation
16:00	Hilde Nilsen
	DNA and RNA quality control by SMUG1
16:25	Ingrun Alseth
	Human Endonuclease V as an inosine specific ribonulclease
16:40	Coffee
16:50	Yungui Yang
	Decipher the biological role of reversible RNA modifications
17:15	Roger Woodgate
	Utilization of Y-family polymerase steric gate mutants to uncover novel mechanisms of ribonucleotide repair
17:40	Hanna Delago
	The DNA repair factor SNEVhPrp19/hPso4 regulates cellular and organismal life span and promotes adipogenic differentiation
17:55	Simon Bekker-Jensen
	SCAI interacts with 53BP1 to promote heterochromatin-associated DNA repair and maintain genomic stability in vivo
18:10	Tapas
Session II: Evening Keynote Presentations
	Chair: Magnar Bjørås
19:00	Miroslav Radman
	Anti-oxidant protection and radiation resistance
19:30	Hans Krokan
	All the things U are
20:00	Matthias Meyer
	Post-mortem DNA damage – challenges to ancient DNA research
Thursday, June 18th 2015
07:30	Breakfast
Session I: RNA Metabolism et al
	Chair: Arne Klungland
09:00	Chuan He
	Oxidative demethylation of RNA in Biological regulation
Session III: Translesion synthesis and mutagenesis associated processes
	Chair: Richard Wood
09:25	Richard Wood
	Suppression of Chromosome instability by DNA polymerase Q
09:50	Graham Walker
	Translesion DNA polymerases: From cancer chemotherapy to bactericidal antibiotics
10:15	Robert Fuchs
	Damaged DNA Replication: how lesion tolerance pathways are interconnected in vivo
10:40	Coffee break
11:10	Arthur Grollman
	Signature mutation of a novel human carcinogen
11:35	Lawrence A. Loeb
	The Mutator Phenotype in Human Cancer
12:00	Eugenia Dogliotti
	Mitochondrial dysfunction in DNA repair defective disorders: mechanisms and pathological relevance
12:25	Matthias Altmeyer
	DNA strand breaks trigger phase transitions of intrinsically disordered proteins
12:40	Françoise Dantzer
	Poly(ADP-ribose polymerase 3 (PARP3) in epithelial to mesenchymal transition
13:00	Lunch
Session IV: DNA repair and disease
	Chair: Eugenia Dogliotti
14:00	Zhao-Qi Wang
	Life without proper DNA repair
14:25	Jan H. J. Hoeijmakers
	The overwhelming role of DNA damage in the process of ageing
14:50	Alan Lehmann
	Genetic and clinical heterogeneity in the XP population in the UK
15:15	Francesco Blasi
	Prep1 (pKnox1) tumor suppressor prevents DNA replication stress, DNA damage and in cancer
15:40	Coffee break/waffles
16:10	Thomas Helleday
	Targeting DNA repair for cancer treatment: from PARP to MTH1 inhibitors
16:35	Ketan J Patel
	Why mammals require DNA crosslink repair
17:00	Peter Karran
	Protein oxidation and human DNA repair
17:25	Alan Tomkinson
	Targeting cancer cell mitochondria
17:50	Posters and refreshments
19:30	Dinner
Friday, June 19th 2015
07:30	Breakfast
Session V: DNA strand breaks and human disease
	Chair: Stephen West
09:00	Stephen West
	Mechanism of Holliday junction resolution by GEN1
09:25	Keith Caldecott
	DNA Strand Break Repair and Human Genetic Disease
09:50	Steve Jackson
	DNA double-strand break repair: a 20/20 vision
10:15	Valentyn Oksenych
	Deficiency of Ku70 rescues early postnatal lethality of XLF/DNA-PKcs double deficient mice
10:30	HaiLin Wang
	ATPase activity-regulated and unbound nucleotide sites-predominated RecA nucleofilaments are the active form for accurate homology recombination
10:45	Coffee
Session VI: The transcription machinery
	Chair: Jean Marc Egly
11:00	Jean Marc Egly
	Involvement of NER factors in transcription
11:25	Moshe Yaniv
	Chromatin remodeling: from transcription to cancer
11:50	Philip Hanawalt
	Consequences of arrested transcription - the good, the bad and the ugly
12:15	Jesper Svejstrup
	The transcription-related DNA damage response
12:40	Joanna Timmins
	Structural and functional studies of NER and HR processes in the extreme-radiation resistant bacterium D. radiodurans
13:00	Lunch
	Afternoon/evening free for sightseeing
Saturday, June 20th 2015
07:30	Breakfast
Session VII: DNA repair and the cell cycle
	Chair: Jiri Bartek
09:00	Jiri Bartek
	DNA damage signalling: Mechanistic insights and relevance for cancer
09:25	Ian D. Hickson
	How unfinished business from S-phase affects mitosis
09:50	Marco Foiani
	Mechanisms controlling the integrity of replicating chromosomes
10:15	Xinzhi (Xavier) Xu
	Regulation of CLASPIN-mediated CHK1 activation
10:40	Fabrizio d'Adda di Fagagna
	The role of RNA in the DNA damage response
11:05	Coffee
Session VIII: Mismatch repair
	Chair: Josef Jiricny
11:25	Josef Jiricny
	Multifaceted mismatch repair
11:50	Margherita Bignami
	Role of MUTYH in human cancer
12:15	Bruce Demple
	When DNA repair goes wrong: Formation and resolution of BER-generated protein-DNA crosslinks with oxidative lesion
12:30	Bernd Kaina
	DNA repair and ROS sensitivity of monocytes, macrophages and other immunocompetent cells
12:45	Manju Hingorani
	A dynamic process of mismatch recognition leads to a stalled MutS-MutL complex for initiation of DNA repair
13:00	Lunch
Session IX: Base excision repair (et al)
	Chair: Primo Schär
14:00	Primo Schär
	Active DNA demethylation by DNA repair - What is it good for?
14:25	Grigory Dianov
	DNA base excision repair
14:55	Geir Slupphaug
	Novel aspects of genomic uracil induction and processing
15:20	Coffee
15:40	Cristina Rada
	Uracil excision in the immune response
16:05	Eric Gilson
	How telomeres exert their influence genome-wide
Session X: EMBO editor
	Chair: Arne Klungland
16:30	Bernd Pulverer
	Transparent Publishing: How to Share Reproducible Data
17:20	Break
18:45	Champagne
Session XI: Tomas Lindahl
19:00	Tomas Lindahl
	Instability, decay and repair of DNA
20:00	Gala dinner
Sunday, June 21th 2015
07:30	Breakfast and departure