Impact of two DNA repair pathways, homologous recombination and non-homologous end joining, on bacterial spore inactivation under simulated martian environmental conditions

Icarus ◽  
2011 ◽  
Vol 215 (1) ◽  
pp. 204-210 ◽  
Author(s):  
Ralf Moeller ◽  
Andrew C. Schuerger ◽  
Günther Reitz ◽  
Wayne L. Nicholson
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Environmental Conditions ◽  
Bacterial Spore ◽  
End Joining ◽  
Repair Pathways ◽  
Non Homologous End Joining

scholarly journals Genome Instability and Pressure on Non-Homologous end Joining drives Chemotherapy Resistance via a DNA Repair Crisis Switch in Triple Negative Breast Cancer.

2020 ◽  
Author(s):  
Adrian Wiegmans ◽  
Ambber Ward ◽  
Ekaterina Ivanova ◽  
Pascal H G Duijf ◽  
Romy VanOosterhout ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Genome Instability ◽  
Chemotherapy Resistance ◽  
End Joining ◽  
Repair Pathways ◽  
Non Homologous End Joining

Abstract Background: Chemotherapy intensifies pressure on the DNA repair pathways that can lead to deregulation. There is an urgent clinical need to be able to track the emergence of chemotherapy resistance and tailor patient staging appropriately. This is especially evident in the triple negative breast cancer (TNBC) subtype, of which standard of care is chemotherapy with tumours displaying high levels of inherent genome instability. TNBC has an overall poor prognosis for survival. There have been numerous studies into single agent chemoresistance but to date no study has elucidated in detail the roles of the key DNA repair components in resistance associated with the frontline clinical combination of anthracyclines and taxanes together. Methods: In this study, we hypothesized that the emergence of chemotherapy resistance is driven by changes in functional signaling in the DNA repair pathways. We identified the importance of the DNA repair pathways in chemoresistant clinical samples and characterized the emergence of chemoresistance in TNBC cell lines. We utilized classical DNA repair assays and specific targeting of key DNA repair proteins to elucidate a new mechanism for adaptation to the combination of doxorubicin and docetaxel. Results: We identified that consistent pressure on the non-homologous end joining pathway in the presence of genome instability causes failure of the key kinase DNA-PK, loss of p53 and compensation by p73. In-turn a switch to reliance on the homologous recombination pathway and RAD51 recombinase occurs to repair residual double strand DNA breaks. Conclusions: We demonstrate that RAD51 is an actionable target for resensitization to chemotherapy in resistant cells with a matched gene expression profile of resistance highlighted by homologous recombination.

scholarly journals Genome instability and pressure on non-homologous end joining drives chemotherapy resistance via a DNA repair crisis switch in triple negative breast cancer

NAR Cancer ◽  
2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Adrian P Wiegmans ◽  
Ambber Ward ◽  
Ekaterina Ivanova ◽  
Pascal H G Duijf ◽  
Mark N Adams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Genome Instability ◽  
Chemotherapy Resistance ◽  
End Joining ◽  
Repair Pathways ◽  
Non Homologous End Joining

Abstract Chemotherapy is used as a standard-of-care against cancers that display high levels of inherent genome instability. Chemotherapy induces DNA damage and intensifies pressure on the DNA repair pathways that can lead to deregulation. There is an urgent clinical need to be able to track the emergence of DNA repair driven chemotherapy resistance and tailor patient staging appropriately. There have been numerous studies into chemoresistance but to date no study has elucidated in detail the roles of the key DNA repair components in resistance associated with the frontline clinical combination of anthracyclines and taxanes together. In this study, we hypothesized that the emergence of chemotherapy resistance in triple negative breast cancer was driven by changes in functional signaling in the DNA repair pathways. We identified that consistent pressure on the non-homologous end joining pathway in the presence of genome instability causes failure of the key kinase DNA-PK, loss of p53 and compensation by p73. In-turn a switch to reliance on the homologous recombination pathway and RAD51 recombinase occurred to repair residual double strand DNA breaks. Further we demonstrate that RAD51 is an actionable target for resensitization to chemotherapy in resistant cells with a matched gene expression profile of resistance highlighted by homologous recombination in clinical samples.

scholarly journals Determination of the DNA repair pathways utilised by acute lymphoblastic leukaemia cells following daunorubicin treatment

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hussain Mubarak Al-Aamri ◽  
Helen R. Irving ◽  
Terri Meehan-Andrews ◽  
Christopher Bradley
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Cell Lines ◽  
Dna Lesions ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Dsb Repair ◽  
Histone H2ax ◽  
Repair Pathways ◽  
Non Homologous End Joining

Abstract Objective DNA double strand breaks (DNA-DSBs) are among the most lethal DNA lesions leading to genomic instability and repaired by either homologous recombination (HR) or the non-homologous end joining (NHEJ) mechanisms. The purpose of this study was to assess the importance and the level of activation of non-homologous end joining (NHEJ) and homologous recombination (HR) DNA repair pathways in three cell lines, CCRF-CEM and MOLT-4 derived from T lymphocytes and SUP-B15 derived from B lymphocytes following treatment with chemotherapy agent daunorubicin. Results The Gamma histone H2AX (γH2AX) assay was used assess the effects of DNA-PK inhibitor NU7026 and RAD51 inhibitor RI-2 on repair of DNA-DSB following treatment with daunorubicin. In all cell lines, the NHEJ DNA repair pathway appeared more rapid and efficient. MOLT-4 and CCFR-CEM cells utilised both NHEJ and HR pathways for DNA-DSB repair. Whereas, SUP-B15 cells utilised only NHEJ for DSB repair, suggestive of a deficiency in HR repair pathways.

Homologous recombination and non-homologous end-joining repair pathways in bovine embryos with different developmental competence

2012 ◽  
Vol 318 (16) ◽  
pp. 2049-2058 ◽  
Author(s):  
Marcos Henrique Barreta ◽  
Bernardo Garziera Gasperin ◽  
Vitor Braga Rissi ◽  
Matheus Pedrotti de Cesaro ◽  
Rogério Ferreira ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Developmental Competence ◽  
Bovine Embryos ◽  
End Joining ◽  
Repair Pathways ◽  
Non Homologous End Joining

scholarly journals Recent Perspectives in Radiation-Mediated DNA Damage and Repair: Role of NHEJ and Alternative Pathways

2021 ◽  
Author(s):  
Ajay Kumar Sharma ◽  
Priyanka Shaw ◽  
Aman Kalonia ◽  
M.H. Yashavarddhan ◽  
Pankaj Chaudhary ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Double Strand Breaks ◽  
Single Strand ◽  
End Joining ◽  
Strand Breaks ◽  
Single Strand Annealing ◽  
Repair Pathways ◽  
Non Homologous End Joining ◽  
Alternative Nhej

Radiation is one of the causative agents for the induction of DNA damage in biological systems. There is various possibility of radiation exposure that might be natural, man-made, intentional, or non-intentional. Published literature indicates that radiation mediated cell death is primarily due to DNA damage that could be a single-strand break, double-strand breaks, base modification, DNA protein cross-links. The double-strand breaks are lethal damage due to the breakage of both strands of DNA. Mammalian cells are equipped with strong DNA repair pathways that cover all types of DNA damage. One of the predominant pathways that operate DNA repair is a non-homologous end-joining pathway (NHEJ) that has various integrated molecules that sense, detect, mediate, and repair the double-strand breaks. Even after a well-coordinated mechanism, there is a strong possibility of mutation due to the flexible nature in joining the DNA strands. There are alternatives to NHEJ pathways that can repair DNA damage. These pathways are alternative NHEJ pathways and single-strand annealing pathways that also displayed a role in DNA repair. These pathways are not studied extensively, and many reports are showing the relevance of these pathways in human diseases. The chapter will very briefly cover the radiation, DNA repair, and Alternative repair pathways in the mammalian system. The chapter will help the readers to understand the basic and applied knowledge of radiation mediated DNA damage and its repair in the context of extensively studied NHEJ pathways and unexplored alternative NHEJ pathways.

scholarly journals ATM antagonizes NHEJ proteins assembly and DNA-ends synapsis at single-ended DNA double strand breaks

2020 ◽  
Vol 48 (17) ◽  
pp. 9710-9723
Author(s):  
Sébastien Britton ◽  
Pauline Chanut ◽  
Christine Delteil ◽  
Nadia Barboule ◽  
Philippe Frit ◽  
...  
Keyword(s):  
Dna Repair ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Strand Breaks ◽  
Repair Pathways ◽  
Non Homologous End Joining ◽  
Dna Strand ◽  
Dna Ends

Abstract Two DNA repair pathways operate at DNA double strand breaks (DSBs): non-homologous end-joining (NHEJ), that requires two adjacent DNA ends for ligation, and homologous recombination (HR), that resects one DNA strand for invasion of a homologous duplex. Faithful repair of replicative single-ended DSBs (seDSBs) is mediated by HR, due to the lack of a second DNA end for end-joining. ATM stimulates resection at such breaks through multiple mechanisms including CtIP phosphorylation, which also promotes removal of the DNA-ends sensor and NHEJ protein Ku. Here, using a new method for imaging the recruitment of the Ku partner DNA-PKcs at DSBs, we uncover an unanticipated role of ATM in removing DNA-PKcs from seDSBs in human cells. Phosphorylation of DNA-PKcs on the ABCDE cluster is necessary not only for DNA-PKcs clearance but also for the subsequent MRE11/CtIP-dependent release of Ku from these breaks. We propose that at seDSBs, ATM activity is necessary for the release of both Ku and DNA-PKcs components of the NHEJ apparatus, and thereby prevents subsequent aberrant interactions between seDSBs accompanied by DNA-PKcs autophosphorylation and detrimental commitment to Lig4-dependent end-joining.

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