{"id":16896,"date":"2015-11-01T11:42:40","date_gmt":"2015-11-01T08:42:40","guid":{"rendered":"http:\/\/109.232.216.219\/~bilimvegelecek\/?p=16896"},"modified":"2018-01-17T11:54:52","modified_gmt":"2018-01-17T08:54:52","slug":"2015-nobel-kimya-odulu-dna-onarim-mekanizmalarinin-kesfi","status":"publish","type":"post","link":"https:\/\/bilimvegelecek.com.tr\/index.php\/2015\/11\/01\/2015-nobel-kimya-odulu-dna-onarim-mekanizmalarinin-kesfi","title":{"rendered":"2015 Nobel Kimya \u00d6d\u00fcl\u00fc:\u00a0DNA onar\u0131m mekanizmalar\u0131n\u0131n ke\u015ffi"},"content":{"rendered":"

Tomas Lindahl, Aziz Sancar ve Paul Modrich h\u00fccrenin kendi DNA\u2019s\u0131n\u0131 onarma mekanizmalar\u0131n\u0131 ortaya \u00e7\u0131karmalar\u0131ndan ve bu sayede genetik bilgilerin nas\u0131l korunabildi\u011fini a\u00e7\u0131klamalar\u0131ndan dolay\u0131 2015 Nobel Kimya \u00d6d\u00fcl\u00fc\u2019ne lay\u0131k g\u00f6r\u00fcld\u00fcler. Aziz Sancar\u2019la birlikte, bilim alan\u0131nda ilk kez bir T\u00fcrk biliminsan\u0131 \u00f6d\u00fcl ald\u0131\u011f\u0131 i\u00e7in, Nobel Kimya \u00d6d\u00fcl\u00fc\u2019n\u00fcn \u00fclkemizdeki yank\u0131s\u0131 g\u00fc\u00e7l\u00fc oldu. <\/em><\/p>\n

\u0130sve\u00e7 Kraliyet Bilim Akademisi, 2015 Nobel Kimya \u00d6d\u00fcl\u00fc\u2019n\u00fc aralar\u0131nda bir T\u00fcrk\u2019\u00fcn de bulundu\u011fu \u00fc\u00e7 biliminsan\u0131na verdi. \u0130ngiltere\u2019deki Francis Crick Enstit\u00fcs\u00fc ve Clare Hall Laboratuvar\u0131\u2019nda \u00e7al\u0131\u015fan Tomas Lindahl, Amerika\u2019daki Howard Hughes T\u0131p Enstit\u00fcs\u00fc ve Duke \u00dcniversitesi T\u0131p Fak\u00fcltesi\u2019nde \u00e7al\u0131\u015fan Paul Modrich ve Amerika\u2019daki Kuzey Carolina \u00dcniversitesi T\u0131p Fak\u00fcltesi\u2019nde \u00e7al\u0131\u015fan Aziz Sancar, h\u00fccrenin kendi DNA\u2019s\u0131n\u0131 nas\u0131l tamir etti\u011fi ve bu sayede genetik bilgilerini nas\u0131l koruyabildi\u011fine dair a\u00e7\u0131klamalar\u0131 ve haritalamalar\u0131ndan dolay\u0131 bu \u00f6d\u00fcle lay\u0131k g\u00f6r\u00fcld\u00fcler.<\/p>\n

\u0130nsan\u0131 insan yapan \u00f6zellikler, 23 kromozomlu spermle 23 kromozomlu yumurtan\u0131n birle\u015fimiyle ortaya \u00e7\u0131k\u0131yor. Birlikte, genom ad\u0131n\u0131 verdi\u011fimiz, her insanda korunmu\u015f olarak bulunan bu genetik materyali olu\u015fturuyorlar. Organlar\u0131m\u0131z, sa\u00e7lar\u0131m\u0131z, derimize kadar her \u015fey bu birle\u015fimden ortaya \u00e7\u0131kan ilk h\u00fccreden, onun i\u00e7inde yer alan DNA materyalinden geli\u015ferek ger\u00e7ekle\u015fiyor. Daha sonra bu h\u00fccrenin b\u00f6l\u00fcnmelerinden ve farkl\u0131la\u015fmalar\u0131ndan yola \u00e7\u0131karak, her h\u00fccre i\u00e7inde ayn\u0131 genetik materyali de bar\u0131nd\u0131rarak geli\u015fim s\u00fcr\u00fcyor. V\u00fccudumuzda ger\u00e7ekle\u015fen kimyasal olaylar mutasyonlarla ba\u015f etmek zorunda ve bu durum DNA i\u00e7in de ge\u00e7erli. DNA, zararl\u0131 radyasyona ve reaktif molek\u00fcllere kar\u015f\u0131 devaml\u0131 tehlike alt\u0131nda.<\/p>\n

Ama DNA\u2019m\u0131z, molek\u00fcler onar\u0131m mekanizmalar\u0131 sayesinde senelerce yap\u0131s\u0131 bozulmadan kendini korumay\u0131 ba\u015far\u0131yor. Bu mekanizmadaki proteinler s\u00fcrekli olarak genom \u00fczerinde dola\u015farak onu herhangi bir darbeye kar\u015f\u0131 korumakla g\u00f6revli.<\/p>\n

DNA\u2019n\u0131n onar\u0131m mekanizmas\u0131n\u0131 molek\u00fcler seviyede g\u00f6stermeyi ba\u015faran Tomas Lindahl, Paul Modrich ve Aziz Sancar\u2019\u0131n sistematik \u00e7al\u0131\u015fmalar\u0131 sayesinde, ya\u015fayan h\u00fccrelerinin fonksiyonlar\u0131n\u0131 nas\u0131l s\u00fcrd\u00fcrd\u00fc\u011f\u00fc, kal\u0131tsal pek \u00e7ok hastal\u0131\u011f\u0131n molek\u00fcler seviyede nedeni, kanser geli\u015fimi ve ya\u015flanman\u0131n mekanizmalar\u0131 gibi pek \u00e7ok alanda kesin sonu\u00e7lara dayal\u0131 bilgiler elde edilebildi. \u00dc\u00e7 biliminsan\u0131 da, birbirlerinden ba\u011f\u0131ms\u0131z olarak insanlarla alakal\u0131 pek \u00e7ok DNA onar\u0131m a\u015famalar\u0131n\u0131 haritalad\u0131lar. Bu \u00fc\u00e7 biliminsan\u0131n\u0131n \u00e7al\u0131\u015fma alanlar\u0131, Tomas Lindahl ile ba\u015flar.<\/p>\n

\"\"Tomas Lindahl:\u00a0 Baz \u00e7\u0131kar\u0131ml\u0131 tamir mekanizmas\u0131n\u0131 buldu<\/strong><\/p>\n

Amerikal\u0131 Tomas Lindahl, 1960\u2019l\u0131 y\u0131llarda DNA\u2019n\u0131n ne kadar stabil olabildi\u011fini sorgulamaya ba\u015flad\u0131. O zamanlardaki bilimsel kurulu\u015flar DNA\u2019n\u0131n diren\u00e7li oldu\u011fu bilgisinden \u00f6teye gitmeye gerek duymayarak bu konuya odaklanmam\u0131\u015flard\u0131. Lindahl, Amerika\u2019da Princeton \u00dcniversitesi\u2019nde doktora sonras\u0131 \u00e7al\u0131\u015fmalar\u0131n\u0131 yapmaktayken, DNA\u2019yla kuzen olan RNA molek\u00fcl\u00fcn\u00fc \u00e7al\u0131\u015fmaktayd\u0131. RNA, DNA\u2019dan \u00e7ok daha hassas bir molek\u00fcld\u00fc, Lindahl bunu, RNA\u2019y\u0131 \u0131s\u0131t\u0131nca molek\u00fcl\u00fcn par\u00e7aland\u0131\u011f\u0131n\u0131 g\u00f6zlemleyerek g\u00f6rd\u00fc; DNA\u2019ya bu kadar yak\u0131n olan RNA molek\u00fcl\u00fcn bu kadar kolay par\u00e7alanmas\u0131 merak\u0131n\u0131 ate\u015fledi ve DNA\u2019n\u0131n nas\u0131l ya\u015fam s\u00fcresince kendini korumay\u0131 ba\u015farabildi\u011fini sorgulamas\u0131na yol a\u00e7t\u0131.<\/p>\n

Bu s\u0131ralarda \u0130sve\u00e7\u2019e ta\u015f\u0131nd\u0131 ve Stockholm\u2019de Karolinska Enstit\u00fcs\u00fc\u2019nde \u00e7al\u0131\u015fmaya ba\u015flad\u0131. Akl\u0131ndaki sorulara y\u00f6nelik yapt\u0131\u011f\u0131 birka\u00e7 deney sonucunda g\u00f6rd\u00fc ki, DNA yava\u015f ama yads\u0131namayacak bir bozulma ya\u015f\u0131yordu. Lindahl, genomun her g\u00fcn y\u00fcz binlerce yaralanmaya maruz kald\u0131\u011f\u0131n\u0131 d\u00fc\u015f\u00fcnerek, DNA\u2019n\u0131n b\u00fct\u00fcn bu yaralar\u0131n\u0131 onaracak birtak\u0131m molek\u00fcler sistemler olmas\u0131 gerekti\u011fini \u00f6ne s\u00fcrd\u00fc ve b\u00f6ylece koskoca yeni bir ara\u015ft\u0131rma alan\u0131n\u0131n kap\u0131lar\u0131n\u0131 a\u00e7t\u0131.<\/p>\n

Lindahl, insan DNA\u2019s\u0131na \u00e7ok benzeyen ve ayn\u0131 \u015fekilde adenin, timin, guanin, sitozin bazlar\u0131ndan olu\u015fan n\u00fckleotidlere sahip bakteri DNA\u2019s\u0131n\u0131 kullanarak, DNA onar\u0131m\u0131nda g\u00f6rev alan tamir enzimlerini aramaya ba\u015flad\u0131. DNA kimyasal olarak zay\u0131fl\u0131\u011f\u0131na sebep olan bir duruma g\u00f6re, sitozin bazl\u0131 amino grubunu kaybetmeye fazla meyilli oldu\u011fundan, b\u00f6yle bir durumda genetik bilgide de\u011fi\u015fimlere sebep oluyor. DNA\u2019n\u0131n \u00e7ift sarmal yap\u0131s\u0131nda, sitozin her zaman guanin ile e\u015fle\u015fir, ancak amino grubunu kaybeden bir sitozin, bu kez adenin baz\u0131yla e\u015fle\u015fiyor. E\u011fer bu de\u011fi\u015fim onar\u0131lmadan devam ederse, DNA\u2019n\u0131n bir dahaki replikasyonunda mutasyona sebep olur. Lindahl h\u00fccrenin bu probleme kar\u015f\u0131 bir korumas\u0131 oldu\u011funu ke\u015ffetti ve amino grubu kopan sitozinleri DNA\u2019dan kald\u0131ran bir bakteriyel enzim bulmay\u0131 ba\u015fard\u0131. \u00c7al\u0131\u015fmas\u0131n\u0131 1974\u2019te yay\u0131mlad\u0131.<\/p>\n

35 y\u0131ll\u0131k ba\u015far\u0131l\u0131 bir \u00e7al\u0131\u015fman\u0131n ilk ad\u0131m\u0131 olan bu \u00e7al\u0131\u015fmas\u0131na \u0130ngiltere\u2019de devam ederek, Francis Crick Enstit\u00fcs\u00fc\u2019nde Clare Hall Laboratuvar\u0131\u2019n\u0131n y\u00f6neticisi oldu. Daha sonraki senelerde DNA onar\u0131m\u0131nda g\u00f6rev alan pek \u00e7ok proteini de buldu. Buldu\u011fu bu enzimlere benzer i\u015flevi olan glikozilaz enzimlerinin g\u00f6rev ald\u0131\u011f\u0131 baz \u00e7\u0131kar\u0131ml\u0131 (eksizyon, kesip \u00e7\u0131karma) tamir mekanizmas\u0131n\u0131n molek\u00fcler g\u00f6sterimini buldu. Baz \u00e7\u0131kar\u0131ml\u0131 tamir insanlarda da olan bir mekanizma olmakla birlikte, Lindahl 1996\u2019da insanlardaki tamir mekanizmas\u0131n\u0131 laboratuvar ortam\u0131nda yapay olarak olu\u015fturmay\u0131 ba\u015fard\u0131.\"\"<\/p>\n

\"\"Aziz Sancar: N\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 tamir mekanizmas\u0131n\u0131 buldu<\/strong><\/p>\n

Tomas Lindahl\u2019\u0131n ara\u015ft\u0131rmalar\u0131nda belirleyici bir fakt\u00f6r, DNA\u2019n\u0131n kendi h\u00fccresi i\u00e7inde korunakl\u0131 \u00e7evre ko\u015fullar\u0131ndayken bile de\u011fi\u015fimler ge\u00e7irdi\u011fini fark etmek oldu. Ancak, DNA\u2019n\u0131n UV radyasyon gibi \u00e7evresel fakt\u00f6rlerden dolay\u0131 hasara u\u011frad\u0131\u011f\u0131 bilinmekteydi. UV radyasyonuyla olu\u015fan hasar\u0131 gidermede pek \u00e7ok h\u00fccre taraf\u0131ndan kullan\u0131lan n\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 (eksizyon) tamir Amerika\u2019da ya\u015famakta olan Aziz Sancar taraf\u0131ndan haritalanarak g\u00f6sterildi.<\/p>\n

Aziz Sancar, \u0130stanbul T\u0131p Fak\u00fcltesi\u2019nde okumu\u015f Mardin do\u011fumlu bir biliminsan\u0131. Mezun olduktan sonra birka\u00e7 y\u0131l Mardin\u2019de pratisyen hekim olarak \u00e7al\u0131\u015ft\u0131, ancak daha \u00fcniversite y\u0131llar\u0131ndayken biyokimyaya ilgi duymaya ba\u015flad\u0131. Bu alana ilgisini tam anlam\u0131yla y\u00f6nlendirmesine sebep olan olay \u015fuydu: Bakterilerin \u00f6l\u00fcmc\u00fcl dozlarda UV radyasyonuna maruz kalmalar\u0131na ra\u011fmen, e\u011fer g\u00f6zle g\u00f6r\u00fcl\u00fcr mavi \u0131\u015f\u0131kla tedavi edilirlerse iyile\u015fmeyi ba\u015farmalar\u0131. Sancar bu sihirli olay\u0131n i\u015flevsel olarak nas\u0131l ger\u00e7ekle\u015fti\u011fini \u00f6\u011frenmek isteyerek ilgisini bu do\u011frultuda yo\u011funla\u015ft\u0131rd\u0131. B\u00f6ylece Aziz Sancar, bu fenomene yo\u011funla\u015fan Claud Rupert adl\u0131 Amerikal\u0131 ara\u015ft\u0131rmac\u0131n\u0131n Dallas\u2019taki Teksas \u00dcniversitesi\u2019ndeki laboratuvar\u0131na kat\u0131ld\u0131. 1976\u2019da, o zaman\u0131n teknolojisiyle, UV hasarl\u0131 DNA\u2019y\u0131 tamir etmede g\u00f6rev alan fotoliyaz enziminin genini klonlamay\u0131 ba\u015fararak ve bu geni laboratuvar ko\u015fullar\u0131nda bakterilere aktararak enzimi y\u00fcksek miktarda \u00fcretmeyi ba\u015fard\u0131.<\/p>\n

Bu \u00e7al\u0131\u015fmas\u0131 doktora tezini yazmas\u0131 i\u00e7in yeterli oldu\u011fu halde, Sancar bu alandaki \u00e7al\u0131\u015fmalar\u0131na devam etmek istedi. Doktora sonras\u0131 e\u011fitimi i\u00e7in ba\u015fvurular\u0131 reddedildi\u011finden, Yale \u00dcniversitesi\u2019nde teknisyen olarak i\u015fe girdi ve DNA tamiri \u00fczerine yapmak istedi\u011fi laboratuvar \u00e7al\u0131\u015fmalar\u0131na burada devam edebildi. Burada ba\u015flatt\u0131\u011f\u0131 \u00e7al\u0131\u015fmalar\u0131 Nobel Kimya \u00d6d\u00fcl\u00fc ile sonu\u00e7land\u0131.<\/p>\n

Bakterilerin UV hasar\u0131n\u0131 tamir etmek i\u00e7in kulland\u0131\u011f\u0131 iki mekanizmas\u0131 oldu\u011fu o zamanlar kesin olarak bilinmekteydi; bunlardan biri \u0131\u015f\u0131\u011fa ba\u011f\u0131ml\u0131 fotoliyaz sisteminin yan\u0131 s\u0131ra, ikinci bir sistem olan karanl\u0131kta i\u015flevsel olan bir tamir mekanizmas\u0131 ke\u015ffedilmi\u015fti. Aziz Sancar\u2019\u0131n Yale \u00dcniversitesi\u2019ndeki i\u015f arkada\u015flar\u0131 1960\u2019lardan beri karanl\u0131k sistemdeki mekanizmay\u0131 \u00e7al\u0131\u015fmaktayd\u0131lar ve bunun i\u00e7in \u00fc\u00e7 farkl\u0131 mutasyona sahip UV\u2019ye duyarl\u0131 bakterileri kullanarak \u00fc\u00e7 fakl\u0131 genetik \u00e7e\u015fitlili\u011fi ayr\u0131 ayr\u0131 incelemekteydiler.<\/p>\n

\"\"Fotoliyaz ile ilgili \u00f6nceki \u00e7al\u0131\u015fmalar\u0131ndaki gibi, Sancar karanl\u0131k sistemin molek\u00fcler mekanizmas\u0131n\u0131 ara\u015ft\u0131rmaya ba\u015flad\u0131. Birka\u00e7 y\u0131l i\u00e7inde bu mutasyona sebep olan \u00fc\u00e7 genin enzimlerini tan\u0131mlay\u0131p, izole edip, karakterize etmeyi ba\u015fard\u0131. Laboratuvar ortam\u0131nda yapay olarak ger\u00e7ekle\u015ftirdi\u011fi \u00e7\u0131\u011f\u0131r a\u00e7an deneyleriyle bu enzimlerin DNA \u00fczerindeki UV hasar\u0131n\u0131 tan\u0131mlad\u0131klar\u0131n\u0131, tespit ettikleri yerdeki DNA zincirini iki taraf\u0131ndan da kestiklerini ke\u015ffetti. Hasarl\u0131 k\u0131sm\u0131 da kapsayan 12-13 n\u00fckleotidlik bir k\u0131sm\u0131n b\u00f6ylece kopar\u0131ld\u0131\u011f\u0131n\u0131 g\u00f6zlemledi. Bu \u00e7al\u0131\u015fmalar\u0131n\u0131 1983\u2019te yay\u0131mlad\u0131.<\/p>\n

Bu ke\u015fif ara\u015ft\u0131rma alan\u0131nda b\u00fcy\u00fck bir de\u011fi\u015fikli\u011fe yol a\u00e7t\u0131. Bu ba\u015far\u0131s\u0131 sayesinde Kuzey Carolina \u00dcniversitesi\u2019nde biyokimya alan\u0131nda do\u00e7ent olarak i\u015f teklifi ald\u0131. Burada ayn\u0131 hassasiyetle n\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 tamir mekanizmas\u0131n\u0131n DNA\u2019y\u0131 kesme a\u015famas\u0131ndan sonraki a\u015famalar\u0131n\u0131 da haritalad\u0131. Tomas Lindahl\u2019\u0131n da aralar\u0131nda oldu\u011fu pek \u00e7ok ara\u015ft\u0131rmac\u0131n\u0131n \u00e7al\u0131\u015fmalar\u0131na paralel olarak, Aziz Sancar n\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 tamir mekanizmas\u0131n\u0131n insanlarda nas\u0131l i\u015fledi\u011fini ara\u015ft\u0131rd\u0131. \u0130nsanlardaki UV hasarl\u0131 DNA tamir mekanizmas\u0131 bakterilere k\u0131yasla daha kompleks olmas\u0131na ra\u011fmen, kimyasal olarak mekanizma b\u00fct\u00fcn organizmalarda benzer \u015fekilde ilerliyor.<\/p>\n

B\u00f6ylece Aziz Sancar, fotoliyaz enzimine geri d\u00f6nerek, bu enzimin bakteriyi iyile\u015ftirmede izledi\u011fi mekanizmay\u0131 ara\u015ft\u0131rd\u0131. Buna ek olarak insanlarda fotoliyaz enzimine e\u015fde\u011fer olan enzimin, insanlar\u0131n biyolojik saatleriyle ili\u015fkili oldu\u011funu ke\u015ffetti.<\/p>\n

\"\"<\/p>\n

\"\"Paul Modrich: Yanl\u0131\u015f e\u015fle\u015fme tamir mekanizmas\u0131n\u0131 buldu<\/strong><\/p>\n

Paul Modrich, Kimya Nobel \u00d6d\u00fcl\u00fcn\u00fc Tomas Lindahl ve Aziz Sancar ile payla\u015fan 3. biliminsan\u0131, Amerika\u2019da New Mexico\u2019nun k\u00fc\u00e7\u00fck bir \u015fehrinde d\u00fcnyaya geldi. Zamanla do\u011faya olan ilgisi artt\u0131 ve bir g\u00fcn biyoloji \u00f6\u011fretmeni olan babas\u0131 ona DNA ile ilgili \u015feyleri \u00e7al\u0131\u015fmas\u0131n\u0131 \u00f6nerdi. Bu d\u00f6nem, 1963 y\u0131l\u0131, James Watson ve Fransis Crick\u2019in DNA\u2019n\u0131n yap\u0131s\u0131n\u0131 ke\u015ffetti\u011fi i\u00e7in Nobel \u00d6d\u00fcl\u00fc ald\u0131\u011f\u0131 zamana tekab\u00fcl ediyordu.<\/p>\n

\u0130lerleyen y\u0131llarda Modrich DNA\u2019ya gitgide artan bir ilgi duymaya ba\u015flad\u0131. Ara\u015ft\u0131rma kariyerinde Stanford \u00dcniversitesi\u2019nde doktora yaparken, Harvard\u2019da doktora sonras\u0131 e\u011fitimi yaparken ve Duke \u00dcniversitesi\u2019nde do\u00e7entlik yaparken DNA\u2019y\u0131 etkileyen pek \u00e7ok enzimi inceledi. 1970\u2019lerin sonuna do\u011fru ilgisini dam metilaz ad\u0131nda bir enzime y\u00f6nlendirdi. Bu enzimin g\u00f6revi DNA\u2019ya metil gruplar\u0131n\u0131 eklemek. Modrich, bu metil gruplar\u0131n\u0131n DNA\u2019y\u0131 i\u015faretlemede kullan\u0131ld\u0131\u011f\u0131n\u0131, bu sayede birtak\u0131m restriksiyon enzimlerine yard\u0131m ederek DNA\u2019n\u0131n do\u011fru yerlerden kesilmesini sa\u011flad\u0131\u011f\u0131n\u0131 g\u00f6rd\u00fc. Ancak sadece birka\u00e7 y\u0131l \u00f6nce, Harvard \u00dcniversitesi\u2019nden bir molek\u00fcler biyolog olan Matther Meselson, DNA\u2019daki metil gruplar\u0131 i\u00e7in farkl\u0131 bir sinyal i\u015flevi modelini \u00f6nermi\u015fti.<\/p>\n

Meselson\u00a0 molek\u00fcler biyoloji becerilerini kullanarak bakterilere \u00f6zel, DNA\u2019s\u0131nda yanl\u0131\u015f bazlarla e\u015fle\u015fmi\u015f dizilime sahip (\u00f6rne\u011fin; adenin-timin e\u015fle\u015fmesi yerine adenin-sitozin e\u015fle\u015fmesi gibi) bir vir\u00fcs geli\u015ftirdi.\u00a0 Bu vir\u00fcs\u00fc bakteriye\u00a0 enjekte etti\u011finde bakteri bu yanl\u0131\u015f e\u015fle\u015fmeleri d\u00fczeltmeyi ba\u015fard\u0131. Bakterinin b\u00f6yle bir fonksiyonu neden geli\u015ftirdi\u011fi bilinmiyordu, ancak 1976\u2019da Meselson bunun DNA e\u015fle\u015fmesi s\u0131ras\u0131nda yanl\u0131\u015f e\u015fle\u015fmeleri d\u00fczelten bir tamir mekanizmas\u0131ndan kaynaklanabilece\u011finden \u015f\u00fcphelendi. Meselson buradan yola \u00e7\u0131karak, DNA \u00fczerindeki metil gruplar\u0131n\u0131n, bakterinin DNA tamiri s\u0131ras\u0131nda hangi DNA zincirini \u015fablon olarak kullanmas\u0131n\u0131 belirtmek i\u00e7in bir i\u015faret olarak kullan\u0131labilece\u011fi fikrini \u00f6nerdi. B\u00f6ylece \u015fablon yani do\u011fru olan zincir metil ile i\u015faretlenmi\u015f, hatal\u0131 zincir ise i\u015faretlenmemi\u015f oluyor, b\u00f6ylelikle hangi zincirin tamir edilece\u011fine dair bir sinyal verilmi\u015f oluyordu.<\/p>\n

Paul Modrich ve Matthew Meselson\u2019un yollar\u0131 bu sayede kesi\u015fti ve birlikte \u00e7al\u0131\u015farak DNA\u2019s\u0131 \u00fczerinde yanl\u0131\u015f e\u015fle\u015fmeler bulunan bir vir\u00fcs dizayn ettiler. Modrich\u2019in dam metilaz enzimi de dahil edilerek yap\u0131lan deneyde, vir\u00fcs bakteriye sald\u0131rd\u0131\u011f\u0131nda, enzimin bakterinin hatal\u0131 zincirine metil grubu ekledi\u011fi, bakterinin de metil grubu olmayan DNA zincirini d\u00fczeltti\u011fini g\u00f6zlemlediler. Modrich ve Meselson\u2019un sonucuna g\u00f6re DNA yanl\u0131\u015f e\u015fle\u015fme tamirinin, DNA e\u015fle\u015firken ger\u00e7ekle\u015fen do\u011fal bir mekanizma oldu\u011fu, bu mekanizman\u0131n da metillenmemi\u015f DNA zincirinin de\u011fi\u015fimiyle i\u015fledi\u011fi ke\u015ffedildi.<\/p>\n

Paul Modrich i\u00e7in bu ke\u015fif bir\u00e7ok sistematik \u00e7al\u0131\u015fmay\u0131 ba\u015flatt\u0131, yanl\u0131\u015f e\u015fle\u015fme tamiri a\u015famalar\u0131nda g\u00f6rev alan enzimleri ard\u0131 ard\u0131na klonlayarak ve haritalayarak \u00e7al\u0131\u015fmalar s\u00fcrd\u00fcr\u00fcld\u00fc. 1980\u2019lerin sonuna do\u011fru buldu\u011fu ve 1989\u2019da yay\u0131mlanan \u00e7al\u0131\u015fmas\u0131nda, bu kompleks molek\u00fcler tamir mekanizmas\u0131n\u0131 laboratuvar ko\u015fullar\u0131nda yapay olarak ger\u00e7ekle\u015ftirmeyi ba\u015fard\u0131 ve detayl\u0131 bir \u015fekilde inceledi.<\/p>\n

Paul Modrich daha sonras\u0131nda bu mekanizman\u0131n insan h\u00fccrelerindeki versiyonunu da \u00e7al\u0131\u015ft\u0131, t\u0131pk\u0131 Tomas Lindahl ve Aziz Sancar gibi. Bug\u00fcn, insan genomu kopyalan\u0131rken olu\u015fan hatalar\u0131n yanl\u0131\u015f e\u015fle\u015fme tamir mekanizmas\u0131 taraf\u0131ndan d\u00fczeltildi\u011fini biliyoruz; ancak insan yanl\u0131\u015f e\u015fle\u015fme tamir mekanizmas\u0131nda h\u00e2l\u00e2 orjinal zincirin tam olarak nas\u0131l tan\u0131mland\u0131\u011f\u0131 bilinmemekte. DNA metilasyonu, bakterilerden farkl\u0131 olarak insan genomu \u00fczerinde pek \u00e7ok farkl\u0131 g\u00f6revde rol al\u0131r. Bu y\u00fczden ayr\u0131ca birtak\u0131m fakt\u00f6rlerin DNA zincirini tan\u0131mlamakta kullan\u0131ld\u0131\u011f\u0131 d\u00fc\u015f\u00fcn\u00fclmekte.<\/p>\n

DNA korumas\u0131nda baz \u00e7\u0131kar\u0131ml\u0131 tamir, n\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 tamir ve yanl\u0131\u015f e\u015fle\u015fme tamiri d\u0131\u015f\u0131nda da pek \u00e7ok mekanizma g\u00f6rev almakta. G\u00fcne\u015f, sigara, genotoksik maddeler gibi pek \u00e7ok fakt\u00f6r\u00fcn sebep oldu\u011fu DNA hasarlar\u0131 her g\u00fcn tamir edilmekte. E\u011fer bu tamir mekanizmalar\u0131ndan yaln\u0131zca biri bile \u00e7\u00f6kerse, genetik bilgi de\u011fi\u015fikli\u011fe u\u011frar ve kanser riski artar. \u00d6rne\u011fin, n\u00fckleotid \u00e7\u0131kar\u0131ml\u0131 tamir a\u015famas\u0131nda olu\u015fan do\u011fu\u015ftan gelen hasarlar, bu bireylerin UV radyasyonuna kar\u015f\u0131 a\u015f\u0131r\u0131 hassas olmalar\u0131na ve g\u00fcne\u015fe maruz kald\u0131klar\u0131nda cilt kanseri olmalar\u0131na sebep oluyor. Bir ba\u015fka \u00f6rnek olarak, DNA yanl\u0131\u015f e\u015fle\u015fme tamiri sistemindeki aksakl\u0131klar kal\u0131tsal kolon kanserine sebep oluyor.<\/p>\n

Kanserin pek \u00e7ok formunda bu tamir mekanizmalar\u0131ndan bir veya birka\u00e7\u0131 k\u0131smen ya da tamamen \u00e7al\u0131\u015fmaz haldedir. Bu nedenle kanser h\u00fccrelerinin DNA\u2019s\u0131 stabil kalamaz ve s\u00fcrekli mutasyon ge\u00e7irip kemoterapiye bile diren\u00e7lerini koruyabilmelerine sebep olur. Bu kanserli h\u00fccreler, h\u00fccrede var olan di\u011fer tamir mekanizmalar\u0131na daha da ba\u011f\u0131ml\u0131 haldedir. Tamir mekanizmalar\u0131n\u0131n hepsinin ortadan kalkmas\u0131, kanserli h\u00fccrelerin \u00f6l\u00fcm\u00fcne sebep oluyor. Ara\u015ft\u0131rmac\u0131lar, kansere kar\u015f\u0131 ila\u00e7 geli\u015ftirirken bu zay\u0131fl\u0131ktan yola \u00e7\u0131k\u0131yorlar. Kalan tamir sistemlerini engellemek, kanserli h\u00fccrenin b\u00fcy\u00fcmesini yava\u015flat\u0131r ve hatta durdurur.<\/p>\n

Sonu\u00e7 olarak, 2015 Kimya Nobel \u00d6d\u00fcl\u00fcne lay\u0131k g\u00f6r\u00fclen bu ke\u015fifler yaln\u0131zca canl\u0131lar\u0131n temel i\u015fleyi\u015fleri hakk\u0131nda de\u011fil, ayn\u0131 zamanda hayat kurtaran tedavilerde de geli\u015fime \u00f6nc\u00fcl\u00fck etmi\u015ftir ve edecektir.<\/p>\n

\"\"<\/p>\n","protected":false},"excerpt":{"rendered":"

Tomas Lindahl, Aziz Sancar ve Paul Modrich h\u00fccrenin kendi DNA\u2019s\u0131n\u0131 onarma mekanizmalar\u0131n\u0131 ortaya \u00e7\u0131karmalar\u0131ndan ve bu sayede genetik bilgilerin nas\u0131l korunabildi\u011fini a\u00e7\u0131klamalar\u0131ndan dolay\u0131 2015 Nobel Kimya \u00d6d\u00fcl\u00fc\u2019ne lay\u0131k g\u00f6r\u00fcld\u00fcler. Aziz Sancar\u2019la birlikte, bilim alan\u0131nda ilk kez bir T\u00fcrk biliminsan\u0131 \u00f6d\u00fcl ald\u0131\u011f\u0131 i\u00e7in, Nobel Kimya \u00d6d\u00fcl\u00fc\u2019n\u00fcn \u00fclkemizdeki yank\u0131s\u0131 g\u00fc\u00e7l\u00fc oldu. \u0130sve\u00e7 Kraliyet Bilim Akademisi, 2015 Nobel […]<\/p>\n","protected":false},"author":662,"featured_media":16897,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[178,21,22,231],"tags":[272,321,541,629,1600],"class_list":["post-16896","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-141-sayi","category-biyoloji","category-kimya","category-molekuler-biyoloji-ve-genetik","tag-dna","tag-kimya","tag-molekuler-biyoloji","tag-nobel","tag-radyasyon"],"acf":[],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t