Histone modifications and their role in epigenetics of cancer

2021 ◽  
Vol 28 ◽  
Author(s):  
Sumera Zaib ◽  
Nehal Rana ◽  
Imtiaz Khan
Keyword(s):  
Histone Modifications ◽  
Cell Function ◽  
Contributing Factors ◽  
Histone Proteins ◽  
Dna Repair Mechanisms ◽  
Current Review ◽  
Lysine Residues ◽  
Repair Mechanisms ◽  
Enhanced Expression

: Epigenetic regulations play a crucial role in the expression of various genes that are important in the normal cell function. Any alteration in these epigenetic mechanisms can lead to the modification of histone and DNA resulting in the silencing or enhanced expression of some genes causing various diseases. Acetylation, methylation, ribosylation or phosphorylation of histone proteins modifies its interaction with the DNA, consequently changing the ratio of heterochromatin and euchromatin. Terminal lysine residues of histone proteins serve as potential targets of such epigenetic modifications. The current review focuses on the histone modifications, their contributing factors, role of these modifications on metabolism leading to cancer and methylation of histone in cancer affects the DNA repair mechanisms.

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 Response in Multiple Myeloma: The Role of the Tumor Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 504
Author(s):  
Takayuki Saitoh ◽  
Tsukasa Oda
Keyword(s):  
Multiple Myeloma ◽  
Dna Damage ◽  
Dna Repair ◽  
Tumor Microenvironment ◽  
Dna Damage Response ◽  
Genetic Instability ◽  
Dna Repair Mechanisms ◽  
Damage Response ◽  
Repair Mechanisms

Multiple myeloma (MM) is an incurable plasma cell malignancy characterized by genomic instability. MM cells present various forms of genetic instability, including chromosomal instability, microsatellite instability, and base-pair alterations, as well as changes in chromosome number. The tumor microenvironment and an abnormal DNA repair function affect genetic instability in this disease. In addition, states of the tumor microenvironment itself, such as inflammation and hypoxia, influence the DNA damage response, which includes DNA repair mechanisms, cell cycle checkpoints, and apoptotic pathways. Unrepaired DNA damage in tumor cells has been shown to exacerbate genomic instability and aberrant features that enable MM progression and drug resistance. This review provides an overview of the DNA repair pathways, with a special focus on their function in MM, and discusses the role of the tumor microenvironment in governing DNA repair mechanisms.

scholarly journals ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination deficient cells

2020 ◽  
Author(s):  
Priyanka Verma ◽  
Yeqiao Zhou ◽  
Zhendong Cao ◽  
Peter V. Deraska ◽  
Moniher Deb ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Parp Inhibitor ◽  
Resistance Mechanisms ◽  
Chromatin Accessibility ◽  
New Approach ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Mutant Cells ◽  
Distinct Aspect

AbstractThe response to Poly (ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair mechanisms and the abundance of lesions that trap PARP enzymes on chromatin. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR based screen, we identify the PAR-binding Snf2-like ATPase, ALC1/CHD1L, as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of BRCA mutant cells and enhanced their sensitivity to PARPi by up to 250-fold, while overcoming several known resistance mechanisms. ALC1 loss was not epistatic to other repair pathways that execute the PARPi response. Instead, ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of repair factors. This resulted in an accumulation of replication associated DNA damage and a reliance on HR. These findings establish PAR-dependent chromatin remodeling as a mechanistically distinct aspect of PARPi responses, implicating ALC1 inhibition as a new approach to overcome therapeutic resistance in HR-deficient cancers.

scholarly journals Nuclear and Mitochondrial DNA Repair in Selected Eukaryotic Aging Model Systems

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Ricardo Gredilla ◽  
Christian Garm ◽  
Tinna Stevnsner
Keyword(s):  
Dna Repair ◽  
Aging Process ◽  
Model Systems ◽  
Genetic Studies ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms ◽  
Mitochondrial Dna Repair ◽  
Aging Mechanisms ◽  
Eukaryotic Organisms

Knowledge about the different mechanisms underlying the aging process has increased exponentially in the last decades. The fact that the basic mechanisms involved in the aging process are believed to be universal allows the use of different model systems, from the simplest eukaryotic cells such as fungi to the most complex organisms such as mice or human. As our knowledge on the aging mechanisms in those model systems increases, our understanding of human aging and the potential interventions that we could approach rise significantly. Among the different mechanisms that have been implicated in the aging process, DNA repair is one of the processes which have been suggested to play an important role. Here, we review the latest investigations supporting the role of these mechanisms in the aging process, stressing how beneficial the use of different model systems is. We discuss how human genetic studies as well as several investigations on mammalian models and simpler eukaryotic organisms have contributed to a better understanding of the involvement of DNA repair mechanisms in aging.

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