scholarly journals Archaea: A Gold Mine for Topoisomerase Diversity

2021 ◽  
Vol 12 ◽  
Author(s):  
Florence Garnier ◽  
Mohea Couturier ◽  
Hélène Débat ◽  
Marc Nadal

The control of DNA topology is a prerequisite for all the DNA transactions such as DNA replication, repair, recombination, and transcription. This global control is carried out by essential enzymes, named DNA-topoisomerases, that are mandatory for the genome stability. Since many decades, the Archaea provide a significant panel of new types of topoisomerases such as the reverse gyrase, the type IIB or the type IC. These more or less recent discoveries largely contributed to change the understanding of the role of the DNA topoisomerases in all the living world. Despite their very different life styles, Archaea share a quasi-homogeneous set of DNA-topoisomerases, except thermophilic organisms that possess at least one reverse gyrase that is considered a marker of the thermophily. Here, we discuss the effect of the life style of Archaea on DNA structure and topology and then we review the content of these essential enzymes within all the archaeal diversity based on complete sequenced genomes available. Finally, we discuss their roles, in particular in the processes involved in both the archaeal adaptation and the preservation of the genome stability.

Cell ◽  
1990 ◽  
Vol 62 (3) ◽  
pp. 403-406 ◽  
Author(s):  
James C. Wang ◽  
Paul R. Caron ◽  
Raymond A. Kim

1990 ◽  
Vol 18 (9) ◽  
pp. 2801-2806 ◽  
Author(s):  
O.I. Kovalsky ◽  
S.A. Kozyavkin ◽  
A.I. Slesarev

Abstract ATP-dependent type I topoisomerases from extremely thermophllic archaebacterla - reverse gyrases - drive positive supercoiling of DNA. We showed that reverse gyrase from Desulfurococcus amylolytlcus breaks the DNA at specific sites and covalentty binds to the 5′ end. In 30 out of 31 sites located in pBR322 DNA fragments, cleavage occurs at the sequence 5′–CNNN∣–(N is any base). The same rule was previously shown to hold for single-stranded DNA breakage by eubacterial topoisomerases I. The relative cleavage frequencies at different sites depend on Mg 2+ and temperature. We discuss the possible physiological and mechanistic role of the above specificity of the bacterial topoisomerases I.


1993 ◽  
Vol 13 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
K M Sheehan ◽  
M R Lieber

V(D)J recombination in lymphoid cells is a site-specific process in which the activity of the recombinase enzyme is targeted to signal sequences flanking the coding elements of antigen receptor genes. The order of the steps in this reaction and their mechanistic interdependence are important to the understanding of how the reaction fails and thereby contributes to genomic instability in lymphoid cells. The products of the normal reaction are recombinant joints linking the coding sequences of the receptor genes and, reciprocally, the signal ends. Extrachromosomal substrate molecules were modified to inhibit the physical synapsis of the recombination signals. In this way, it has been possible to assess how inhibiting the formation of one joint affects the resolution efficiency of the other. Our results indicate that signal joint and coding joint formation are resolved independently in that they can be uncoupled from each other. We also find that signal synapsis is critical for the generation of recombinant products, which greatly restricts the degree of potential single-site cutting that might otherwise occur in the genome. Finally, inversion substrates manifest synaptic inhibition at much longer distances than do deletion substrates, suggesting that a parallel rather than an antiparallel alignment of the signals is required during synapsis. These observations are important for understanding the interaction of V(D)J signals with the recombinase. Moreover, the role of signal synapsis in regulating recombinase activity has significant implications for genome stability regarding the frequency of recombinase-mediated chromosomal translocations.


Author(s):  
Chenzhong Xu ◽  
Jin Zhang ◽  
Jie Zhang ◽  
Baohua Liu

AbstractN-acetyltransferase 10 catalyzes RNA N4-acetylcytidine (ac4C) modifications and thus regulates RNA stability and translation efficiency. However, the deacetylase for ac4C is unknown. SIRT7 was initially identified as an NAD+-dependent protein deacetylase and plays essential roles in genome stability, circadian rhythms, metabolism, and aging. In this study, we identified SIRT7 as a deacetylase of the ac4C of ribosomal (r)RNA for the first time and found it to be NAD+-independent. Our data highlight the important role of SIRT7 in rRNA ac4C modification and suggest an additional epitranscriptional regulation of aging.


2021 ◽  
Author(s):  
Bing Sun ◽  
McLean Sherrin ◽  
Richard Roy

Abstract During periods of starvation organisms must modify both gene expression and metabolic pathways to adjust to the energy stress. We previously reported that C. elegans that lack AMPK have transgenerational reproductive defects that result from abnormally elevated H3K4me3 levels in the germ line following recovery from acute starvation1. Here we show that H3K4me3 is dramatically increased at promoters, driving aberrant transcription elongation that results in the accumulation of R-loops in the starved AMPK mutants. DRIP-seq analysis demonstrated that a significant proportion of the genome was affected by R-loop formation with a dramatic expansion in the number of R-loops at numerous loci, most pronounced at the promoter-TSS regions of genes in the starved AMPK mutants. The R-loops are transmissible into subsequent generations, likely contributing to the transgenerational reproductive defects typical of these mutants following starvation. Strikingly, AMPK null germ lines show considerably more RAD-51 foci at sites of R-loop formation, potentially sequestering it from its critical role at meiotic breaks and/or at sites of induced DNA damage. Our study reveals a previously unforeseen role of AMPK in maintaining genome stability following starvation, where in its absence R-loops accumulate, resulting in reproductive compromise and DNA damage hypersensitivity.


Author(s):  
Uwe Weissflog

Abstract This paper provides an overview of methods and ideas to achieve data integration in CIM. It describes a dictionary approach allowing participating applications to define their common constructs gradually as an additional service across application systems. Because of the importance of product definition data, the role of PDES/STEP as part of this dictionary approach is also described. The technical concepts of the dictionary, such as schema mapping, semantic data model, user methods and the required additions within participating applications are explained. Problems related to data integrity, data redundancy, performance and binding of dissimilar software components are discussed as well as the deficiencies related to today’s data modelling capabilities. The added value an active dictionary can provide to a CIM environment consisting of established applications in heterogeneous environments, where migration into one standardized homogeneous set of CIM applications is not likely, is also explained.


2018 ◽  
Vol 19 (11) ◽  
pp. 3569 ◽  
Author(s):  
Lilas Courtot ◽  
Jean-Sébastien Hoffmann ◽  
Valérie Bergoglio

Genome stability requires tight regulation of DNA replication to ensure that the entire genome of the cell is duplicated once and only once per cell cycle. In mammalian cells, origin activation is controlled in space and time by a cell-specific and robust program called replication timing. About 100,000 potential replication origins form on the chromatin in the gap 1 (G1) phase but only 20–30% of them are active during the DNA replication of a given cell in the synthesis (S) phase. When the progress of replication forks is slowed by exogenous or endogenous impediments, the cell must activate some of the inactive or “dormant” origins to complete replication on time. Thus, the many origins that may be activated are probably key to protect the genome against replication stress. This review aims to discuss the role of these dormant origins as safeguards of the human genome during replicative stress.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miaomiao Bai ◽  
Dongdong Ti ◽  
Qian Mei ◽  
Jiejie Liu ◽  
Xin Yan ◽  
...  

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.


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