Involvement of Nucleotide Excision and Mismatch Repair Mechanisms in Double Strand Break Repair

Zhang, Ye; Rohde, Larry H.; Wu, Honglu

doi:10.2174/138920209788488544

Cited by 78 publications

(61 citation statements)

References 119 publications

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“…Deney sonunda hücrelerin mikroskopta elde edilen görüntüleri kuyruklu yıldıza benzemekte ve bu kuyruğun uzunluğu DNA fragmentasyonunun yoğunluğunu göstermektedir [2]. Çeşitli etoposit (1,5,10 …”

Section: Comet Deneyiunclassified

“…İyonize radyasyon, oksidatif stres ve kimyasal ajanlar gibi etkenlerle oluşan DNA çift zincir kırıklarının onarımı serbest uçların non-homolog şekilde bağlanması (NHEJ) ya da homolog rekombinasyon ile olur [1]. DNA çift zincir kırıklarının belirlenmesi ve onarılması hüc-re sağkalımı için gereklidir.…”

Section: Introductionunclassified

“…Non-homolog rekombinasyon gibi bazı onarım mekanizmaları hataya yatkındır ve kırılan bölgelerde genetik bilginin kaybıyla sonuçlanabilir. Çift zincir kı-rıklarının tamirinde en temel mekanizmalardan biri ise homolog rekombinasyondur [1]. Çift zincir DNA kırıklarının NHEJ yolağı ile onarımı DNA bağımlı protein kinaz (DNA-PK) ve DNA ligaz IV-XRCC4 protein kompleksleri aracılığı ile olur.…”

Section: Introductionunclassified

“…Uçlar MRX proteinleri ve DNA ligaz-XRCC4 ile birleştirilir. Eğer hücreler S ya da G2 fazında ise onarım RAD, BRCA1 ve BRCA2'nin görev aldığı homolog rekombinasyon ile olur [1]. Hücre döngüsü sinyallerinin farklı onarım mekanizmalarına nasıl etkilediği halen tam olarak bilinmemektedir.…”

Section: Introductionunclassified

“…Hücre döngüsü sinyallerinin farklı onarım mekanizmalarına nasıl etkilediği halen tam olarak bilinmemektedir. DNA topoizomerazlar DNA'da geçici kırıklar oluşturan ve hücre sağkalımı için gerekli olan ve evrimsel açıdan son derece iyi korunmuş çekirdek enzimleridir [1]. Topoizomeraz I tek zincir kırığı oluştururken, topoizomeraz II ATP kullanarak, çift zincir kırıkları oluşturur ve sarmal DNA'nın çözülmesini sağlar [2].…”

Section: Introductionunclassified

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The Effects of Topoisomerase Inhibition on Dna Repair and Apoptosis in L929 Fibroblasts

Dogan¹,

Yar²,

Ergin³

et al. 2013

Turk J Bioch

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Objective: DNA repair pathways in cells are essential for the maintenance of genome integrity, and for countering the induction of tumorigenesis. Topoisomerase II is a nuclear enzyme that functions during both DNA replication and transcription. The topoisomerase II inhibitor etoposide is an antineoplastic drug that has been used to generate DNA damage and maintain apoptosis. Etoposide blocks cell division by interfering with the topoisomerase II and generates double strand breaks. Application of topoisomerase II inhibitors leads to the formation of double strand breaks that are rapidly repaired following removal of the drug.In the present study, we searched the apoptotic events and early double strand DNA repair process that prevent the apoptotic cell death of L929 fibroblasts in response to treatment with etoposide. Methods: Cytotoxicty of etoposide on L929 cells was determined in a time and dose dependent manner with MTT assay. The double strand DNA breaks were determined with comet assay. Acridin orange/Ethidium bromide fluorescence staining and Caspase 3/7 activity assays were performed in determined etoposide concentrations at 24 hour. Quantitative mRNA expressions of DNA repair genes (Ku70, Ku80, BRCA2, Rad51, XRCC4) were determined after etoposide treatment. Results:The levels of apoptotic cell markers and DNA double strand breaks were elevated in the increasing doses and time. The relative expression levels of Rad51, XRCC4 and BRCA2 were unstable in a time and dose dependent manner. Ku80 levels were generally decreased in etoposide treated groups when compared with controls. However, Ku70 was highly expressed at 9 and 12 hour with the increasing doses. Conclusion: According to the results of this study, etoposide activates apoptotic events. Also, low expression levels of DNA repair enzymes prevent cell survival from DNA damage.

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Section: Comet Deneyiunclassified

Section: Introductionunclassified

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The Effects of Topoisomerase Inhibition on Dna Repair and Apoptosis in L929 Fibroblasts

Dogan¹,

Yar²,

Ergin³

et al. 2013

Turk J Bioch

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Mechanisms of immunogenicity in colorectal cancer

Sillo

Beggs

Morton

et al. 2019

British Journal of Surgery

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Background The immune response in cancer is increasingly understood to be important in determining clinical outcomes, including responses to cancer therapies. New insights into the mechanisms underpinning the immune microenvironment in colorectal cancer are helping to develop the role of immunotherapy and suggest targeted approaches to the management of colorectal cancer at all disease stages. Method A literature search was performed in PubMed, MEDLINE and Cochrane Library databases to identify relevant articles. This narrative review discusses the current understanding of the contributors to immunogenicity in colorectal cancer and potential applications for targeted therapies. Results Responsiveness to immunotherapy in colorectal cancer is non‐uniform. Several factors, both germline and tumour‐related, are potential determinants of immunogenicity in colorectal cancer. Current approaches target tumours with high immunogenicity driven by mutations in DNA mismatch repair genes. Recent work suggests a role for therapies that boost the immune response in tumours with low immunogenicity. Conclusion With the development of promising therapies to boost the innate immune response, there is significant potential for the expansion of the role of immunotherapy as an adjuvant to surgical treatment in colorectal cancer.

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Influence of DNA repair gene polymorphisms on prognosis in inoperable non‐small cell lung cancer patients treated with radiotherapy and platinum‐based chemotherapy

Butkiewicz

Drosik

Suwiński

et al. 2012

Intl Journal of Cancer

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Polymorphisms in DNA repair genes may modulate not only an individual DNA repair capacity, DNA damage levels and cancer risk but also clinical outcome after DNA damage-inducing anticancer therapy. In this study, we analyzed the association between the XPA -4G>A, XPD Asp312Asn, hOGG1 Ser326Cys, XRCC1 Arg399Gln, XRCC2 -4234G>C, XRCC3 -4541A>G and Thr241Met polymorphisms and prognosis in 250 inoperable non-small cell lung cancer (NSCLC) patients treated with radiotherapy and platinum-based chemotherapy. In univariate model, the XPA-4A and XRCC1 399Gln alleles alone and in combination influenced survival only in stage III group. In multivariate analysis, the XPA-4 GA/AA was associated with poor survival (HR 1.55, p 5 0.011 overall and HR 1.72, p 5 0.008 in stage III). In chemoradiotherapy group, the XPA-4A carriers were at increased risk of death and progression (HR 1.73, p 5 0.013 and HR 1.65, p 5 0.016, respectively), especially in stage III (p 5 0.008). Moreover, individuals with ! 2 XPA/XRCC1 adverse alleles showed a higher risk of death (HR 1.46, p 5 0.036 overall; HR 1.85, p 5 0.004 in stage III and HR 1.71, p 5 0.022 in chemoradiotherapy group) and progression (HR 1.75, p 5 0.011 overall and HR 1.93, p 5 0.005 in stage III). The XPA-4 GA/AA genotype individually and together with the XRCC1 399Gln was an independent unfavorable prognostic factor in our study. Thus, our findings indicate a prognostic potential of the XPA-4G>A in unresected NSCLC treated with radiotherapy and chemoradiotherapy. The results require validation in an independent population.

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Involvement of Nucleotide Excision and Mismatch Repair Mechanisms in Double Strand Break Repair

Cited by 78 publications

References 119 publications

The Effects of Topoisomerase Inhibition on Dna Repair and Apoptosis in L929 Fibroblasts

The Effects of Topoisomerase Inhibition on Dna Repair and Apoptosis in L929 Fibroblasts

Mechanisms of immunogenicity in colorectal cancer

Influence of DNA repair gene polymorphisms on prognosis in inoperable non‐small cell lung cancer patients treated with radiotherapy and platinum‐based chemotherapy

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