scholarly journals Tools for Decoding Ubiquitin Signaling in DNA Repair

2021 ◽  
Vol 9 ◽  
Author(s):  
Benjamin Foster ◽  
Martin Attwood ◽  
Ian Gibbs-Seymour
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Dna Lesions ◽  
Post Translational Modifications ◽  
Dna Repair Mechanisms ◽  
Repair Processes ◽  
Repair Mechanisms ◽  
Mechanistic Basis ◽  
Cellular Dna

The maintenance of genome stability requires dedicated DNA repair processes and pathways that are essential for the faithful duplication and propagation of chromosomes. These DNA repair mechanisms counteract the potentially deleterious impact of the frequent genotoxic challenges faced by cells from both exogenous and endogenous agents. Intrinsic to these mechanisms, cells have an arsenal of protein factors that can be utilised to promote repair processes in response to DNA lesions. Orchestration of the protein factors within the various cellular DNA repair pathways is performed, in part, by post-translational modifications, such as phosphorylation, ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs). In this review, we firstly explore recent advances in the tools for identifying factors involved in both DNA repair and ubiquitin signaling pathways. We then expand on this by evaluating the growing repertoire of proteomic, biochemical and structural techniques available to further understand the mechanistic basis by which these complex modifications regulate DNA repair. Together, we provide a snapshot of the range of methods now available to investigate and decode how ubiquitin signaling can promote DNA repair and maintain genome stability in mammalian cells.

scholarly journals Obesity, DNA Damage, and Development of Obesity-Related Diseases

2019 ◽  
Vol 20 (5) ◽  
pp. 1146 ◽  
Author(s):  
Marta Włodarczyk ◽  
Grażyna Nowicka
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genome Stability ◽  
Dietary Habits ◽  
Cell Metabolism ◽  
Cancer Cell Proliferation ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Risk Assessment And Prevention ◽  
And Migration

Obesity has been recognized to increase the risk of such diseases as cardiovascular diseases, diabetes, and cancer. It indicates that obesity can impact genome stability. Oxidative stress and inflammation, commonly occurring in obesity, can induce DNA damage and inhibit DNA repair mechanisms. Accumulation of DNA damage can lead to an enhanced mutation rate and can alter gene expression resulting in disturbances in cell metabolism. Obesity-associated DNA damage can promote cancer growth by favoring cancer cell proliferation and migration, and resistance to apoptosis. Estimation of the DNA damage and/or disturbances in DNA repair could be potentially useful in the risk assessment and prevention of obesity-associated metabolic disorders as well as cancers. DNA damage in people with obesity appears to be reversible and both weight loss and improvement of dietary habits and diet composition can affect genome stability.

scholarly journals Homologous Recombination Repair Polymorphisms and the Risk for Osteosarcoma / Polimorfizam Gena Odgovornih Za Reparaciju Dnk Homolognom Rekombinacijom I Rizikza Pojavu Osteosarkoma

2015 ◽  
Vol 34 (2) ◽  
pp. 200-206 ◽  
Author(s):  
Katja Goričar ◽  
Viljem Kovač ◽  
Janez Jazbec ◽  
Janez Lamovec ◽  
Vita Dolžan
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Genome Stability ◽  
Cancer Susceptibility ◽  
Homologous Recombination Repair ◽  
Nucleotide Polymorphisms ◽  
Dna Repair Mechanisms ◽  
Recombination Repair ◽  
Repair Mechanisms ◽  
Repair Genes

Summary Background: DNA repair mechanisms are essential for maintaining genome stability, and genetic variability in DNA repair genes may contribute to cancer susceptibility. Our aim was to evaluate the influence of polymorphisms in the homologous recombination repair genes XRCC3, RAD51, and NBN on the risk for osteosarcoma. Methods: In total, 79 osteosarcoma cases and 373 controls were genotyped for eight single nucleotide polymorphisms (SNPs) in XRCC3, RAD51, and NBN. Logistic regression was used to determine the association of these SNPs with risk for osteosarcoma. Results: None of the investigated SNPs was associated with risk for osteosarcoma in the whole cohort of patients, however, in patients diagnosed before the age of thirty years XRCC3 rs861539 C>T and NBN rs1805794 G>C were associated with significantly decreased risk for osteosarcoma (P=0.047, OR=0.54, 95% CI=0.30-0.99 and P=0.036, OR=0.42, 95% CI=0.19-0.94, respectively). Moreover, in the carriers of a combination of polymorphic alleles in both SNPs risk for osteosarcoma was decreased even more significantly (Ptrend=0.007). The risk for developing osteosarcoma was the lowest in patients with no wild-type alleles for both SNPs (P=0.039, OR=0.31, 95% CI=0.10-0.94). Conclusions: Our results suggest that polymorphisms in homologous recombination repair genes might contribute to risk for osteosarcoma in patients diagnosed below the age of thirty years.

scholarly journals Take a Break to Repair: A Dip in the World of Double-Strand Break Repair Mechanisms Pointing the Gaze on Archaea

2021 ◽  
Vol 22 (24) ◽  
pp. 13296
Author(s):  
Mariarosaria De Falco ◽  
Mariarita De Felice
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Genome Stability ◽  
Developmental Disorders ◽  
Strand Break ◽  
Human Diseases ◽  
Dna Damages ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Repair Pathways

All organisms have evolved many DNA repair pathways to counteract the different types of DNA damages. The detection of DNA damage leads to distinct cellular responses that bring about cell cycle arrest and the induction of DNA repair mechanisms. In particular, DNA double-strand breaks (DSBs) are extremely toxic for cell survival, that is why cells use specific mechanisms of DNA repair in order to maintain genome stability. The choice among the repair pathways is mainly linked to the cell cycle phases. Indeed, if it occurs in an inappropriate cellular context, it may cause genome rearrangements, giving rise to many types of human diseases, from developmental disorders to cancer. Here, we analyze the most recent remarks about the main pathways of DSB repair with the focus on homologous recombination. A thorough knowledge in DNA repair mechanisms is pivotal for identifying the most accurate treatments in human diseases.

Post-translational modifications of lysine in DNA-damage repair

2012 ◽  
Vol 52 ◽  
pp. 93-111 ◽  
Author(s):  
Snehajyoti Chatterjee ◽  
Parijat Senapati ◽  
Tapas K. Kundu
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Post Translational Modifications ◽  
Dna Repair Mechanisms ◽  
The Past ◽  
Damage Repair ◽  
Lysine Residues ◽  
Repair Mechanisms ◽  
Genotoxic Insult

DNA damage in cells is often the result of constant genotoxic insult. Nevertheless, efficient DNA repair pathways are able to maintain genomic integrity. Over the past decade it has been revealed that it is not only kinase signalling pathways which play a central role in this process, but also the different post-translational modifications at lysine residues of histone (chromatin) and non-histone proteins. These lysine modifications include acetylation, methylation, ubiquitination and SUMOylation. Genomic instability is often the major cause of different diseases, especially cancer, where lysine modifications are altered and thereby have an impact on the various DNA repair mechanisms. This chapter will discuss the recent advances in our understanding of the role of different lysine modifications in DNA repair and its physiological consequences.

scholarly journals DNA Damage: From Threat to Treatment

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1665 ◽  
Author(s):  
Antonio Carusillo ◽  
Claudio Mussolino
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genetic Information ◽  
Dna Lesions ◽  
Interstrand Crosslinks ◽  
Dna Repair Mechanisms ◽  
Abasic Sites ◽  
Damage Sensing ◽  
Repair Mechanisms ◽  
Complete Failure

DNA is the source of genetic information, and preserving its integrity is essential in order to sustain life. The genome is continuously threatened by different types of DNA lesions, such as abasic sites, mismatches, interstrand crosslinks, or single-stranded and double-stranded breaks. As a consequence, cells have evolved specialized DNA damage response (DDR) mechanisms to sustain genome integrity. By orchestrating multilayer signaling cascades specific for the type of lesion that occurred, the DDR ensures that genetic information is preserved overtime. In the last decades, DNA repair mechanisms have been thoroughly investigated to untangle these complex networks of pathways and processes. As a result, key factors have been identified that control and coordinate DDR circuits in time and space. In the first part of this review, we describe the critical processes encompassing DNA damage sensing and resolution. In the second part, we illustrate the consequences of partial or complete failure of the DNA repair machinery. Lastly, we will report examples in which this knowledge has been instrumental to develop novel therapies based on genome editing technologies, such as CRISPR-Cas.

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