Reprogramming and genome integrity: role of non-homologous end joining

Salomoni, Paolo

doi:10.1038/cdd.2013.95

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Furthermore, the limited reprogramming capacity was associated with genomic instability and could be rescued by reintroduction of DNA ligase IV [ 26 ] or genetic complementation [ 28 ]. Interestingly, p53 downregulation did not have any effect on the reprogramming defect in mutated iPSC lines, leading to the possibility that cell death induced by impaired DNA repair in DNA ligase IV-lacking cells could be p53 independent [ 29 ]. It is possible that the stress of reprogramming leads to DNA DBS formation, yet the exact mechanism remains to be elucidated.…”

Section: Dna Damage and Repair Status During Reprogrammingmentioning

confidence: 99%

Stem Cells: The Pursuit of Genomic Stability

Wyles

Brandt

Nelson

2014

IJMS

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Stem cells harbor significant potential for regenerative medicine as well as basic and clinical translational research. Prior to harnessing their reparative nature for degenerative diseases, concerns regarding their genetic integrity and mutation acquisition need to be addressed. Here we review pluripotent and multipotent stem cell response to DNA damage including differences in DNA repair kinetics, specific repair pathways (homologous recombination vs. non-homologous end joining), and apoptotic sensitivity. We also describe DNA damage and repair strategies during reprogramming and discuss potential genotoxic agents that can reduce the inherent risk for teratoma formation and mutation accumulation. Ensuring genomic stability in stem cell lines is required to achieve the quality control standards for safe clinical application.

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Section: Dna Damage and Repair Status During Reprogrammingmentioning

confidence: 99%

Stem Cells: The Pursuit of Genomic Stability

Wyles

Brandt

Nelson

2014

IJMS

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“…One of the critical anticancer functions of PML is to facilitate stabilization of the key tumour suppressor p53 [6,29,30], allowing it to transcriptionally activate growth suppressive targets like p21 [31,32]. This is achieved in response to stress, by PML sequestering p53's major inhibitor Mdm2 to the nucleolus [33] and facilitating p53 to associate with kinases that confer vital stabilizing, post‐translational modifications: homeodomain‐interacting protein kinase‐2 at p53 Ser46 [34], Checkpoint 2 kinase at p53 Ser20 [35] and Casein kinase 1 at p53 Thr18 [36].…”

Section: The Role Of Pml As a Tumour Suppressormentioning

confidence: 99%

PML tumour suppression and beyond: Therapeutic implications

et al. 2014

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a b s t r a c tRecognition of the tumour suppressive capacity of the Promyelocytic Leukemia protein (PML) has emerged beyond its identification through APL, to a broad spectrum of tumors. This ability has chiefly been linked to its role as a core component of dynamic structures termed PML Nuclear Bodies (PML-NBs). In response to a variety of stresses, key factors and their molecular modifiers are recruited to PML-NBs, where activating modifications are facilitated, leading to a cellular stress response. PML was also found to perform anti-tumourigenic functions through cytoplasmic activities. Surprisingly, important recent research defined growth promoting capabilities of PML, which significantly challenges the notion of a 'classic' tumour suppressor. Through metabolic reprogramming, PML can afford a selective advantage for tumor cells in certain settings. The multiple forms in which PML exists are the likely explanation of this functional diversity. This behavioral ambiguity however raises a significant challenge to the design of strategies to therapeutically target PML. In this review we discuss this change of paradigm in the PML field and its ramifications, particularly for tailoring cancer therapies.

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“…Breaks in both strands of DNA, as those caused by ionizing radiations, are the most lethal lesions that cells have to cope with: in fact, if left unrepaired, DSBs can lead to genomic rearrangements and eventually to cell transformation or to cell death. The two main cellular mechanisms to repair DSBs are the Homologous Recombination (HR) and the Non-Homologous End Joining (NHEJ) [ 61 – 63 ] (Figure 2 right ). The HR pathway [ 64 ] provides an accurate repair of DSBs by using the sister chromatid as template.…”

Section: Dsbs Repairmentioning

confidence: 99%

DNA repair and aging: the impact of the p53 family

Nicolai

Rossi

Daniele

et al. 2015

Aging

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Cells are constantly exposed to endogenous and exogenous factors that threaten the integrity of their DNA. The maintenance of genome stability is of paramount importance in the prevention of both cancer and aging processes. To deal with DNA damage, cells put into operation a sophisticated and coordinated mechanism, collectively known as DNA damage response (DDR). The DDR orchestrates different cellular processes, such as DNA repair, senescence and apoptosis. Among the key factors of the DDR, the related proteins p53, p63 and p73, all belonging to the same family of transcription factors, play multiple relevant roles. Indeed, the members of this family are directly involved in the induction of cell cycle arrest that is necessary to allow the cells to repair. Alternatively, they can promote cell death in case of prolonged or irreparable DNA damage. They also take part in a more direct task by modulating the expression of core factors involved in the process of DNA repair or by directly interacting with them. In this review we will analyze the fundamental roles of the p53 family in the aging process through their multifaceted function in DDR.

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Reprogramming and genome integrity: role of non-homologous end joining

Cited by 4 publications

References 7 publications

Stem Cells: The Pursuit of Genomic Stability

Stem Cells: The Pursuit of Genomic Stability

PML tumour suppression and beyond: Therapeutic implications

DNA repair and aging: the impact of the p53 family

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