{"id":"https://openalex.org/G2832582425","display_name":"Kanser Tedavisine Y\u00f6nelik DNA Polimeraz Gama Enzimini Hedefleyerek Mitokondriyel Baz Eksizyon Tamir Mekanizmas\u0131n\u0131 Bloke Eden K\u00fc\u00e7\u00fck Molek\u00fcl \u0130nhibit\u00f6rlerinin Belirlenmesi Ve Etkinliklerinin Saptanmas\u0131","description":"Bir\u00e7ok kemoterap\u00f6tik ajan ve radyasyon sitotoksik etkilerini DNA hasar\u0131n\u0131 ind\u00fckleyerek g\u00f6sterir. Fakat DNA tamir yolaklar\u0131 DNA hasar\u0131na diren\u00e7 g\u00f6stererek bu hasar\u0131n \u00f6ld\u00fcr\u00fcc\u00fc etkilerinden h\u00fccreyi korur ve b\u00f6ylece genomik kararl\u0131l\u0131\u011f\u0131 sa\u011flar. Bu nedenle, kanser h\u00fccresindeki DNA tamir yolaklar\u0131 kanser tedavisinin \u00f6n\u00fcnde \u00e7ok \u00f6nemli bir engeldir. Kanser tedavisinin ba\u015far\u0131l\u0131 olmas\u0131 normal h\u00fccrelere zarar vermeden se\u00e7ici olarak t\u00fcm\u00f6r h\u00fccresinin \u00f6ld\u00fcr\u00fclmesine ba\u011fl\u0131d\u0131r. Bu se\u00e7ici sitotoksisite, DNA tamirine ba\u011fl\u0131 sentetik letal etkile\u015fimler \u00fczerinden ger\u00e7ekle\u015febilir. MLH1 ve DNA polimeraz gama (Polg) aras\u0131ndaki sentetik letal ili\u015fki, MLH1 mutasyonunun dolay\u0131s\u0131yla yanl\u0131\u015f e\u015fle\u015fme tamir hasar\u0131n\u0131n neden oldu\u011fu polipsiz kolorektal kanser (Lynch sendromu) h\u00fccrelerinin, normal h\u00fccrelere zarar vermeden tedavi edilmesini, Polg n\u0131n inhibisyonu ile m\u00fcmk\u00fcn k\u0131lar. Bu projede, Polg y\u0131 dolay\u0131s\u0131yla mitokondriyel BER yola\u011f\u0131n\u0131 inhibe eden yeni k\u00fc\u00e7\u00fck molek\u00fcl inhibit\u00f6r\u00fc(leri) bulmak, etkinli\u011fini saptamak ve tan\u0131mlamak i\u00e7in, bilgisayar ortam\u0131nda (in siliko) molek\u00fcler ``docking`` yakla\u015f\u0131m\u0131 ile ve ila\u00e7 olma olas\u0131l\u0131\u011f\u0131 y\u00fcksek ticari molek\u00fcl k\u00fct\u00fcphanesi k\u00fc\u00e7\u00fck molek\u00fclleri tarand\u0131. K\u00fc\u00e7\u00fck molek\u00fcllerin Pol? proteinine ba\u011flanma kineti\u011fi y\u00fczey plazmon rezonans analizi ile belirlendi. Bu molek\u00fcllerden, obcun19 molek\u00fcl\u00fcn\u00fcn Polg n\u0131n DNA sentez aktivitesini, mitokondriyel BER yola\u011f\u0131n\u0131 inhibe etti\u011fi ve sentetik letal yakla\u015f\u0131m\u0131 ile HCT116 kolon kanser h\u00fccresine se\u00e7ici sitotoksisite g\u00f6sterdi\u011fi belirlendi. Bu molek\u00fcl\u00fcn, MLH1 geni mutant HCT116 h\u00fccrelerinde, MLH1 geni bulunan HCT116chr3(V1) kontrol h\u00fccrelerine k\u0131yasla mitokondriyel apoptozu, mitokondriyel membran potansiyelini art\u0131rd\u0131\u011f\u0131 ve mtDNA da daha fazla oksidatif hasara neden oldu\u011fu g\u00f6sterilmi\u015ftir. Bu veriler, MLH1 mutasyonu nedeniyle olu\u015fan kanserlerin se\u00e7ici tedavisi i\u00e7in obcun19 un, potansiyel yeni bir molek\u00fcl olarak geli\u015ftirilebilece\u011fini g\u00f6stermektedir. Bu nedenle, inhibit\u00f6r\u00fcn in vivo toksisitesini ara\u015ft\u0131rmak i\u00e7in HCT116 h\u00fccresi kullan\u0131larak \u00e7\u0131plak farede ksenograft \u00e7al\u0131\u015fmalar\u0131 ba\u015flat\u0131lm\u0131\u015ft\u0131r.","funder_award_id":"212T026","funder":{"id":"https://openalex.org/F4320322626","display_name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ft\u0131rma Kurumu","doi":"10.13039/501100004410"},"funded_outputs":["https://openalex.org/W3197839892","https://openalex.org/W4282032131","https://openalex.org/W7217970501"],"funded_outputs_count":3,"parent_awards":[],"sub_awards":[],"sub_awards_count":0,"amount":null,"currency":null,"amount_usd":null,"amount_usd_basis":null,"recipients":[],"recipient_countries":[],"recipient_regions":[],"research_scope":{"is_research":true,"basis":"funder_default","tier":1},"funding_type":"research","funder_scheme":"KBAG","start_date":"2013-04-01","end_date":"2016-11-01","start_year":2013,"end_year":2016,"landing_page_url":"https://search.trdizin.gov.tr/tr/yayin/detay/1385930","doi":null,"provenance":"trdizin_tubitak_projects","lead_investigator":{"given_name":"Meltem","family_name":"Muftuoglu","orcid":"0000-0001-5372-4780","role_start":"2013-04-01","affiliation":{"name":null,"country":null,"ids":null}},"co_lead_investigator":null,"investigators":[{"given_name":"batu","family_name":"erman","orcid":"0000-0003-2180-7607","role_start":"2013-04-01","affiliation":{"name":null,"country":null,"ids":null}},{"given_name":"MUSTAFA CENG\u0130Z","family_name":"YAKICIER","orcid":null,"role_start":"2013-04-01","affiliation":{"name":null,"country":null,"ids":null}},{"given_name":"Burak","family_name":"Erman","orcid":null,"role_start":"2013-04-01","affiliation":{"name":null,"country":null,"ids":null}}],"works_api_url":"https://api.openalex.org/works?filter=awards.id:G2832582425","primary_topic":null,"topics":null,"institution_awarded":[],"updated_date":"2026-10-16T03:01:01.000Z","created_date":"2026-07-13T04:53:33.000Z"}