scholarly journals Uracil DNA glycosylase (UNG) loss enhances DNA double strand break formation in human cancer cells exposed to pemetrexed

2014 ◽  
Vol 5 (2) ◽  
pp. e1045-e1045 ◽  
Author(s):  
L D Weeks ◽  
G E Zentner ◽  
P C Scacheri ◽  
S L Gerson
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Strand Break ◽  
Double Strand Break ◽  
Dna Glycosylase ◽  
Uracil Dna Glycosylase ◽  
Human Cancer Cells ◽  
Dna Double Strand Break ◽  
Break Formation

scholarly journals Intrastrand Annealing Leads to the Formation of a Large DNA Palindrome and Determines the Boundaries of Genomic Amplification in Human Cancer

2007 ◽  
Vol 27 (6) ◽  
pp. 1993-2002 ◽  
Author(s):  
Hisashi Tanaka ◽  
Yi Cao ◽  
Donald A. Bergstrom ◽  
Charles Kooperberg ◽  
Stephen J. Tapscott ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Gene Amplification ◽  
Human Cancer ◽  
Strand Break ◽  
Double Strand Break ◽  
Early Event ◽  
Inverted Repeats ◽  
Genomic Amplification ◽  
Dna Double Strand Break ◽  
Dna Palindrome

ABSTRACT Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double-strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and nonrandomly distributed in the genomes of cancer cells and facilitate a further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known how a DSB is resolved to form a large DNA palindrome and whether any local DNA structure determines the location of large DNA palindromes. We show here that intrastrand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determine the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and nonamplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.

Quantification of DNA double-strand break induced by radiation in cervix cancer cells: in vitro study

2018 ◽  
Vol 18 (1) ◽  
pp. 52-54
Author(s):  
Sothing Vashum ◽  
Rabi Raja Singh I ◽  
Saikat Das ◽  
Mohammed Azharuddin KO ◽  
Prabhakaran Vasudevan
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Strand Break ◽  
Double Strand Break ◽  
Ionising Radiation ◽  
Dependent Manner ◽  
Survival Fraction ◽  
Dna Double Strand Break ◽  
Cervical Cancer Cells

AbstractAimDNA double-strand break (DSB) results in the phosphorylation of the protein, H.2AX histone. In this study, the effect of radiotherapy and chemotherapy on DNA DSB in cervical cancer cells is analysed by the phosphorylation of the protein.MethodsThe cervical cancer cells (HeLa cells) were cultured and exposed to ionising radiation. Radiation sensitivity was measured by clonogenic survival fraction after exposing to ionising radiation. Since the phosphorylation of H.2AX declines with time, the DNA damage was quantified at different time points: 1 hour, 3 hours and 1 week after exposed to the radiation. The analysis of γ-H.2AX was done by Western-blot technique. The protein expression was observed at different dose of radiation and combination of both radiation and paclitaxel.ResultsLow-dose hypersensitivity was observed. By 1 week after radiation at 0·5, 0·8 and 2 Gy, there was no expression of phosphorylated H.2AX. Previous experiments on the expression of phosphorylated H.2AX (γ-H.2AX) in terms of foci analysis was found to peak at 1 hour and subsequently decline with time. In cells treated with the DNA damaging agents, the expression of phosphorylated H.2AX decreases in a dose-dependent manner when treated with radiation alone. However, when combined with paclitaxel, at 0·5 Gy, the expression peaked and reduces at 0·8 Gy and slightly elevated at 2 Gy.FindingsIn this study, the peak phosphorylation was observed at 3 hour post irradiation indicating that DSBs are still left unrepaired.

scholarly journals DNA double-strand break repair efficiency in cancer cells exposed to laser-driven ultrashort electron beams

2021 ◽  
Author(s):  
Andreyan Osipov ◽  
Nelly Babayan ◽  
Natalia Vorobyeva ◽  
Bagrat Grigoryan ◽  
Anna Chigasova-Grekhova ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Electron Beams ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Dna Double Strand Break ◽  
Repair Efficiency ◽  
Break Repair

scholarly journals Defining the mutation signatures of DNA polymerase θ in cancer genomes

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Taejoo Hwang ◽  
Shelley Reh ◽  
Yerkin Dunbayev ◽  
Yi Zhong ◽  
Yoko Takata ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Dna Polymerase ◽  
Human Cancer ◽  
Strand Break ◽  
Base Substitution ◽  
Cancer Therapies ◽  
End Joining ◽  
Dsb Repair ◽  
Human Cancer Cells ◽  
Insertion And Deletion

Abstract DNA polymerase theta (POLQ)-mediated end joining (TMEJ) is a distinct pathway for mediating DNA double-strand break (DSB) repair. TMEJ is required for the viability of BRCA-mutated cancer cells. It is crucial to identify tumors that rely on POLQ activity for DSB repair, because such tumors are defective in other DSB repair pathways and have predicted sensitivity to POLQ inhibition and to cancer therapies that produce DSBs. We define here the POLQ-associated mutation signatures in human cancers, characterized by short insertions and deletions in a specific range of microhomologies. By analyzing 82 COSMIC (Catalogue of Somatic Mutations in Cancer) signatures, we found that BRCA-mutated cancers with a higher level of POLQ expression have a greatly enhanced representation of the small insertion and deletion signature 6, as well as single base substitution signature 3. Using human cancer cells with disruptions of POLQ, we further show that TMEJ dominates end joining of two separated DSBs (distal EJ). Templated insertions with microhomology are enriched in POLQ-dependent distal EJ. The use of this signature analysis will aid in identifying tumors relying on POLQ activity.

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