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Kök Hücrelerde DNA Hasarı ve Onarımı

Yıl 2022, Cilt: 5 Sayı: 1, 19 - 26, 30.03.2022

Ceyda Durmaz Esra Şen

Öz

Kök hücreler organizmanın yaşamı boyunca süresiz olarak kendi kendini çoğaltma yeteneğine sahip olan, doğru koşullar altında veya doğru sinyaller verildiğinde, organizmayı oluşturan birçok farklı hücre tipine dönüşebilen yapılardır. Fizyolojik doku homeostazın ve hücreler arası heterojenliğin sağlanmasında kök hücreler büyük önem taşımaktadır. Çeşitli kök hücrelerdeki sayısal veya fonksiyonel bozukluklar, embriyonik letalite, gelişimsel kusurlar, yaşlanmaya bağlı dejeneratif bozukluklar ve onkogenez dahil olmak üzere patofizyolojik koşullarla ilişkilendirilmektedir. Endojen veya eksojen kökenli genetik lezyonlar başlıca kök hücrelerin hayatta kalmasına ve işlevine yönelik tehditler oluşturmaktadır. Hücre içi ve dışı streslerin sebep olduğu değişiklikler sonucunda DNA hasarları ortaya çıkmaktadır. Bu hasar noktalarını onaran tamir mekanizmaları ise genomik kararlığının sürdürülmesinde etki göstermektedir. DNA hasarlarının giderilememesi ve kök hücre bütünlüğünün de bozulması sonucunda hücrenin apoptoza ve yaşlanmaya sürüklenmesine sebebiyet vermektedir. Hücre; genomik bütünlüğü korumak, DNA hasarının zararlı sonuçlarını azaltmak için topluca işlev gören DNA onarımı, hasar toleransı, hücre döngüsü kontrol noktaları ve hücre ölüm yolları gibi mekanizmalar ile donatılmıştır. Ancak organizmada oluşan hasar ve stresi tamir etmede devreye giren hücre içi tamir sistemlerine ek olarak endojen olarak kullanılan antioksidanlar ve farmakolojik ilaçlar da hasarların boyutunu azaltmada etkili olabilmektedir.

Anahtar Kelimeler

Kök Hücre DNA hasarı DNA hasarı onarımı

Kaynakça

  • Goodell MA, Rando TA. Stem cells and healthy aging. Science 2015; 350(6265):1199-1204. doi: 10.1126/science.aab3388.
  • Kreso A, Van Galen P, Pedley NM, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med 2014; 20(1):29-36. doi: 10.1038/nm.3418.
  • Blanpain C, Simons BD. Unravelling stem cell dynamics by lineage tracing. Nat Rev Mol Cell Biol 2013; 14(8):489-502. doi: 10.1038/nrm3625.
  • Blanpain C, Mohrin M, Sotiropoulou PA, et al. DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 2011; 8(1):16-29. doi: 10.1016/j.stem.2010.12.012.
  • Behrens A, Van Deursen JM, Rudolph KL, et al. Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 2014; 16(3):201-207. doi: 10.1038/ncb2928.
  • Kimbrel EA, Lanza R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat Rev Drug Discov 2015; 14(10):681-692. doi: 10.1038/nrd4738.
  • Kapinas K, Grandy R, Ghule P, et al. The abbreviated pluripotent cell cycle. J Cell Physiol 2013; 228(1):9-20. doi: 10.1002/jcp.24104.
  • Ahuja AK, Jodkowska K, Teloni F, et al. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nat Commun 2016; 7(1):1-11. doi: 10.1038/ncomms10660.
  • Maynard S, Swistowska AM, Lee JW, et al. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells 2008; 26(9):2266-2274. doi: 10.1634/stemcells.2007-1041.
  • Liu S, Uppal H, Demaria M, et al. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci Rep 2015; 14(5):17895. doi: 10.1038/srep17895.
  • Li M, He Y, Dubois W, et al. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell 2012; 46(1):30-42. doi: 10.1016/j.molcel.2012.01.020.
  • Gonzales KAU, Liang H, Lim YS, et al. Deterministic restriction on pluripotent state dissolution by cell-cycle pathways. Cell 2015;162(3):564-579. http://dx.doi.org/10.1016/j.cell.2015.07.001.
  • Vitale I, Manic G, De Maria R, et al. DNA damage in stem cells. Mol Cell 2017;66(3):306-319. doi: 10.1016/j.molcel.2017.04.006.
  • Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals. Science 2010;327(5965):542-545. doi: 10.1126/science.1180794.
  • Adams PD, Jasper H, Rudolph KL. Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell 2015; 16(6):601-612. doi: 10.1016/j.stem.2015.05.002.
  • Kowalczyk MS, Tirosh I, Heckl D, et al. Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells. Genome Res 2015; 25(12):1860-1872. doi: 10.1101/gr.192237.115.
  • Zambetti NA, Ping Z, Chen S, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell 2016;19(5):613-627. doi: 10.1016/j.stem.2016.08.021.
  • Beerman I, Seita J, Inlay MA, et al. Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell 2014;15(1):37-50. doi: 10.1016/j.stem.2014.04.016.
  • Wang J, Lu X, Sakk V, et al. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood 2014; 124(22):3237-3240. doi: 10.1182/blood-2014-04-568055.
  • Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med 2011;208(3):455-467. doi: 10.1084/jem.20101145.
  • Mandal PK, Blanpain C, Rossi DJ. DNA damage response in adult stem cells: pathways and consequences. Nat Rev Mol Cell Biol 2011;12(3):198-202. doi: 10.1038/nrm3060.
  • Chang CH, Zhang M, Rajapakshe K, et al. Mammary stem cells and tumor-initiating cells are more resistant to apoptosis and exhibit increased DNA repair activity in response to DNA damage. Stem Cell Reports 2015; 5(3):378-391. doi: 10.1016/j.stemcr.2015.07.009.
  • Sotiropoulou PA, Candi A, Mascré G, et al. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat Cell Biol 2010; 12(6):572-582. doi: 10.1038/ncb2059.
  • Ferdousi LV, Rocheteau P, Chayot R, et al. More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny. Stem Cell Res 2014;13(3):492-507. doi: 10.1016/j.scr.2014.08.005.
  • Ji J, Sharma V, Qi S, et al. Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells. Stem Cell Reports 2014; 2(1):44-51. doi: 10.1016/j.stemcr.2013.11.004.
  • Felgentreff K, Du L, Weinacht KG, et al. Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells. Proc Natl Acad Sci 2014; 111(24):8889-8894. doi: 10.1073/pnas.1323649111.
  • Lamm N, Ben-David U, Golan-Lev T, et al. Genomic instability in human pluripotent stem cells arises from replicative stress and chromosome condensation defects. Cell Stem Cell 2016; 18(2):253-261. doi: 10.1016/j.stem.2015.11.003.
  • Rivlin N, Koifman G, Rotter V. p53 orchestrates between normal differentiation and cancer. Semin Cancer Biol 2015; 32:10-17. doi: 10.1016/j.semcancer.2013.12.006.
  • Dannenmann B, Lehle S, Hildebrand DG, et al. High glutathione and glutathione peroxidase-2 levels mediate cell-type-specific DNA damage protection in human induced pluripotent stem cells. Stem cell reports 2015; 4(5):886-898. doi: 10.1016/j.stemcr.2015.04.004.
  • Krokan HE, Bjoras M. Base excision repair. Cold Spring Harb Perspect Biol 2013; 5(4):a012583. doi: 10.1101/cshperspect.a012583.
  • Kavaklı H, Gül Ş, Berkel Ç, et al. Kanserde Dna Tamiri ve Tedavide Dna Tamir Yolakları. Ed: Yusuf Baran, Kanser Moleküler Biyolojisi. 1. basım. Kısayol matbaacılık; 2018. ss. 173-184.
  • Lee TH, Kang TH. DNA oxidation and excision repair pathways. Int J Mol Sci 2019; 20(23):6092. doi: 10.3390/ijms20236092.
  • Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen 2017; 58(5):235-263. doi: 10.1002/em.22087.
  • Limpose KL, Corbett AH, Doetsch PW. BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management. DNA repair 2017; 56:51-64. doi: 10.1016/j.dnarep.2017.06.007.
  • Kurtoğlu EL, Tekedereli İ. Dna Onarım Mekanizmaları. Balıkesir Sağlık Bil Derg 2015; 4(3):169-177. DOI:10.5505/bsbd.2015.52523.
  • Onur E, Tuğrul B, Bozyiğit F. DNA hasarı ve onarım mekanizmaları. Türk Klinik Biyokimya Derg 2009; 7(2):61-70. pdf_TKB_120.pdf (dergisi.org).
  • Stingele J, Bellelli R, Boulton SJ. Mechanisms of DNA–protein crosslink repair. Nat Rev Mol Cell Biol 2017; 18(9):563-573. doi: 10.1038/nrm.2017.56.

DNA Damage and Repair In Stem Cells

Yıl 2022, Cilt: 5 Sayı: 1, 19 - 26, 30.03.2022

Ceyda Durmaz Esra Şen

Öz

Anahtar Kelimeler

Stem cells DNA damage DNA damage repair

Kaynakça

  • Goodell MA, Rando TA. Stem cells and healthy aging. Science 2015; 350(6265):1199-1204. doi: 10.1126/science.aab3388.
  • Kreso A, Van Galen P, Pedley NM, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med 2014; 20(1):29-36. doi: 10.1038/nm.3418.
  • Blanpain C, Simons BD. Unravelling stem cell dynamics by lineage tracing. Nat Rev Mol Cell Biol 2013; 14(8):489-502. doi: 10.1038/nrm3625.
  • Blanpain C, Mohrin M, Sotiropoulou PA, et al. DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 2011; 8(1):16-29. doi: 10.1016/j.stem.2010.12.012.
  • Behrens A, Van Deursen JM, Rudolph KL, et al. Impact of genomic damage and ageing on stem cell function. Nat Cell Biol 2014; 16(3):201-207. doi: 10.1038/ncb2928.
  • Kimbrel EA, Lanza R. Current status of pluripotent stem cells: moving the first therapies to the clinic. Nat Rev Drug Discov 2015; 14(10):681-692. doi: 10.1038/nrd4738.
  • Kapinas K, Grandy R, Ghule P, et al. The abbreviated pluripotent cell cycle. J Cell Physiol 2013; 228(1):9-20. doi: 10.1002/jcp.24104.
  • Ahuja AK, Jodkowska K, Teloni F, et al. A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nat Commun 2016; 7(1):1-11. doi: 10.1038/ncomms10660.
  • Maynard S, Swistowska AM, Lee JW, et al. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage. Stem Cells 2008; 26(9):2266-2274. doi: 10.1634/stemcells.2007-1041.
  • Liu S, Uppal H, Demaria M, et al. Simvastatin suppresses breast cancer cell proliferation induced by senescent cells. Sci Rep 2015; 14(5):17895. doi: 10.1038/srep17895.
  • Li M, He Y, Dubois W, et al. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell 2012; 46(1):30-42. doi: 10.1016/j.molcel.2012.01.020.
  • Gonzales KAU, Liang H, Lim YS, et al. Deterministic restriction on pluripotent state dissolution by cell-cycle pathways. Cell 2015;162(3):564-579. http://dx.doi.org/10.1016/j.cell.2015.07.001.
  • Vitale I, Manic G, De Maria R, et al. DNA damage in stem cells. Mol Cell 2017;66(3):306-319. doi: 10.1016/j.molcel.2017.04.006.
  • Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals. Science 2010;327(5965):542-545. doi: 10.1126/science.1180794.
  • Adams PD, Jasper H, Rudolph KL. Aging-induced stem cell mutations as drivers for disease and cancer. Cell Stem Cell 2015; 16(6):601-612. doi: 10.1016/j.stem.2015.05.002.
  • Kowalczyk MS, Tirosh I, Heckl D, et al. Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells. Genome Res 2015; 25(12):1860-1872. doi: 10.1101/gr.192237.115.
  • Zambetti NA, Ping Z, Chen S, et al. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human pre-leukemia. Cell Stem Cell 2016;19(5):613-627. doi: 10.1016/j.stem.2016.08.021.
  • Beerman I, Seita J, Inlay MA, et al. Quiescent hematopoietic stem cells accumulate DNA damage during aging that is repaired upon entry into cell cycle. Cell Stem Cell 2014;15(1):37-50. doi: 10.1016/j.stem.2014.04.016.
  • Wang J, Lu X, Sakk V, et al. Senescence and apoptosis block hematopoietic activation of quiescent hematopoietic stem cells with short telomeres. Blood 2014; 124(22):3237-3240. doi: 10.1182/blood-2014-04-568055.
  • Mortensen M, Soilleux EJ, Djordjevic G, et al. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance. J Exp Med 2011;208(3):455-467. doi: 10.1084/jem.20101145.
  • Mandal PK, Blanpain C, Rossi DJ. DNA damage response in adult stem cells: pathways and consequences. Nat Rev Mol Cell Biol 2011;12(3):198-202. doi: 10.1038/nrm3060.
  • Chang CH, Zhang M, Rajapakshe K, et al. Mammary stem cells and tumor-initiating cells are more resistant to apoptosis and exhibit increased DNA repair activity in response to DNA damage. Stem Cell Reports 2015; 5(3):378-391. doi: 10.1016/j.stemcr.2015.07.009.
  • Sotiropoulou PA, Candi A, Mascré G, et al. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat Cell Biol 2010; 12(6):572-582. doi: 10.1038/ncb2059.
  • Ferdousi LV, Rocheteau P, Chayot R, et al. More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny. Stem Cell Res 2014;13(3):492-507. doi: 10.1016/j.scr.2014.08.005.
  • Ji J, Sharma V, Qi S, et al. Antioxidant supplementation reduces genomic aberrations in human induced pluripotent stem cells. Stem Cell Reports 2014; 2(1):44-51. doi: 10.1016/j.stemcr.2013.11.004.
  • Felgentreff K, Du L, Weinacht KG, et al. Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells. Proc Natl Acad Sci 2014; 111(24):8889-8894. doi: 10.1073/pnas.1323649111.
  • Lamm N, Ben-David U, Golan-Lev T, et al. Genomic instability in human pluripotent stem cells arises from replicative stress and chromosome condensation defects. Cell Stem Cell 2016; 18(2):253-261. doi: 10.1016/j.stem.2015.11.003.
  • Rivlin N, Koifman G, Rotter V. p53 orchestrates between normal differentiation and cancer. Semin Cancer Biol 2015; 32:10-17. doi: 10.1016/j.semcancer.2013.12.006.
  • Dannenmann B, Lehle S, Hildebrand DG, et al. High glutathione and glutathione peroxidase-2 levels mediate cell-type-specific DNA damage protection in human induced pluripotent stem cells. Stem cell reports 2015; 4(5):886-898. doi: 10.1016/j.stemcr.2015.04.004.
  • Krokan HE, Bjoras M. Base excision repair. Cold Spring Harb Perspect Biol 2013; 5(4):a012583. doi: 10.1101/cshperspect.a012583.
  • Kavaklı H, Gül Ş, Berkel Ç, et al. Kanserde Dna Tamiri ve Tedavide Dna Tamir Yolakları. Ed: Yusuf Baran, Kanser Moleküler Biyolojisi. 1. basım. Kısayol matbaacılık; 2018. ss. 173-184.
  • Lee TH, Kang TH. DNA oxidation and excision repair pathways. Int J Mol Sci 2019; 20(23):6092. doi: 10.3390/ijms20236092.
  • Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ Mol Mutagen 2017; 58(5):235-263. doi: 10.1002/em.22087.
  • Limpose KL, Corbett AH, Doetsch PW. BERing the burden of damage: Pathway crosstalk and posttranslational modification of base excision repair proteins regulate DNA damage management. DNA repair 2017; 56:51-64. doi: 10.1016/j.dnarep.2017.06.007.
  • Kurtoğlu EL, Tekedereli İ. Dna Onarım Mekanizmaları. Balıkesir Sağlık Bil Derg 2015; 4(3):169-177. DOI:10.5505/bsbd.2015.52523.
  • Onur E, Tuğrul B, Bozyiğit F. DNA hasarı ve onarım mekanizmaları. Türk Klinik Biyokimya Derg 2009; 7(2):61-70. pdf_TKB_120.pdf (dergisi.org).
  • Stingele J, Bellelli R, Boulton SJ. Mechanisms of DNA–protein crosslink repair. Nat Rev Mol Cell Biol 2017; 18(9):563-573. doi: 10.1038/nrm.2017.56.
Toplam 37 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Derleme
Yazarlar

Ceyda Durmaz Bu kişi benim 0000-0002-3588-1798

Esra Şen 0000-0002-3739-3384

Yayımlanma Tarihi 30 Mart 2022
Kabul Tarihi 20 Nisan 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 5 Sayı: 1

Kaynak Göster

APA Durmaz, C., & Şen, E. (2022). Kök Hücrelerde DNA Hasarı ve Onarımı. Tıp Fakültesi Klinikleri Dergisi, 5(1), 19-26.
 Kapak Resmi İndir


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