Mathematical Modeling for DNA Repair, Carcinogenesis and Cancer Detection

Tang, Jonathan; Georgescu, Walter; Deschamps, Thomas; Yannone, Steven M.; Costes, Sylvain V.

doi:10.1007/978-3-319-12136-9_4

Cited by 9 publications

(5 citation statements)

References 118 publications

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“…Although single-strand breaks are easily repaired through excision repair mechanisms (Hall and Giaccia, 2006), double-strand breaks (DSBs) involve more complex repair processes. Risks of misrepair can elicit cell-cycle arrest, cell death, mutations, chromosomal rearrangements (Costes et al, 2010;Sridharan et al, 2015), and subsequent carcinogenesis (Tang et al, 2015).…”

Section: Dna Damagementioning

confidence: 99%

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Afshinnekoo

Scott

MacKay

et al. 2020

Cell

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294

163

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Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

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Section: Dna Damagementioning

confidence: 99%

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Afshinnekoo

Scott

MacKay

et al. 2020

Cell

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294

163

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“…Effective telomere capping of chromosomal ends requires an adequate length of telomere repeats and a highly condensed heterochromatic state 9 27 28 . The loss of either feature impairs protection of the ends and increases the risk of carcinogenesis, presumably through erroneous recognition of chromosome ends as double strand breaks leading to inappropriate DNA double strand break repair 29 30 .…”

Section: Discussionmentioning

confidence: 99%

The Rb1 tumour suppressor gene modifies telomeric chromatin architecture by regulating TERRA expression

Gonzalez-Vasconcellos

Schneider

Anastasov

et al. 2017

Sci Rep

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The tumour suppressor gene (Rb1) is necessary for the maintenance of telomere integrity in osteoblastic cells. We now show that the compaction of telomeric chromatin and the appropriate histone modifications of telomeric DNA are both dependent upon Rb1-mediated transcription of the telomere-derived long non-coding RNA TERRA. Expression of TERRA was reduced in Rb1 haploinsufficient cells, and further decreased by shRNA-mediated reduction of residual Rb1 expression. Restoration of Rb1 levels through lentiviral transduction was sufficient to reestablish both transcription of TERRA and condensation of telomeric chromatin. The human chromosome 15q TERRA promoter contains predicted retinoblastoma control elements, and was able to confer Rb1-dependent transcription upon a promoterless reporter gene. Chromatin immunoprecipitation revealed preferential binding of phosphorylated over non-phosphorylated Rb1 at the TERRA promoter. As Rb1-deficient cells show increased genomic instability we suggest that this novel non-canonical action of Rb1 may contribute to the tumour suppressive actions of Rb1.

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“…The most common source of clustered DNA lesions is ionizing radiation (IR). However, there are many other sources of DSBs, as reviewed by Tang et al [31], such as endogenous stress, which is typically driven by Reactive Oxygen species (ROS) attack, or programmed recombinational events, which purposely introduce DSBs under specific genomic contexts. In the endogenous type of damage, non-DSB lesions (oxypurine or oxypyrimidine base damage or single strand breaks) are prevalent.…”

Section: Damage Inductionmentioning

confidence: 99%

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Nikitaki

Pariset

Sudar

et al. 2020

Cancers

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Complexity of DNA damage is considered currently one if not the primary instigator of biological responses and determinant of short and long-term effects in organisms and their offspring. In this review, we focus on the detection of complex (clustered) DNA damage (CDD) induced for example by ionizing radiation (IR) and in some cases by high oxidative stress. We perform a short historical perspective in the field, emphasizing the microscopy-based techniques and methodologies for the detection of CDD at the cellular level. We extend this analysis on the pertaining methodology of surrogate protein markers of CDD (foci) colocalization and provide a unique synthesis of imaging parameters, software, and different types of microscopy used. Last but not least, we critically discuss the main advances and necessary future direction for the better detection of CDD, with important outcomes in biological and clinical setups.

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Mathematical Modeling for DNA Repair, Carcinogenesis and Cancer Detection

Cited by 9 publications

References 118 publications

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

The Rb1 tumour suppressor gene modifies telomeric chromatin architecture by regulating TERRA expression

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

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