scholarly journals Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins

Archaea ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-24 ◽  
Author(s):  
David S. Shin ◽  
Ashley J. Pratt ◽  
John A. Tainer
Keyword(s):  
Dna Replication ◽  
Environmental Stress ◽  
Stress Responses ◽  
Protein Structures ◽  
Genome Integrity ◽  
Damage Response ◽  
Dna Replication And Repair ◽  
The Face ◽  
Domains Of Life ◽  
Fundamental Systems

As the third domain of life, archaea, like the eukarya and bacteria, must have robust DNA replication and repair complexes to ensure genome fidelity. Archaea moreover display a breadth of unique habitats and characteristics, and structural biologists increasingly appreciate these features. As archaea include extremophiles that can withstand diverse environmental stresses, they provide fundamental systems for understanding enzymes and pathways critical to genome integrity and stress responses. Such archaeal extremophiles provide critical data on the periodic table for life as well as on the biochemical, geochemical, and physical limitations to adaptive strategies allowing organisms to thrive under environmental stress relevant to determining the boundaries for life as we know it. Specifically, archaeal enzyme structures have informed the architecture and mechanisms of key DNA repair proteins and complexes. With added abilities to temperature-trap flexible complexes and reveal core domains of transient and dynamic complexes, these structures provide insights into mechanisms of maintaining genome integrity despite extreme environmental stress. The DNA damage response protein structures noted in this review therefore inform the basis for genome integrity in the face of environmental stress, with implications for all domains of life as well as for biomanufacturing, astrobiology, and medicine.

scholarly journals CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair

2000 ◽  
Vol 113 (15) ◽  
pp. 2647-2658 ◽  
Author(s):  
P. Ridgway ◽  
G. Almouzni
Keyword(s):  
Dna Replication ◽  
Chromatin Assembly ◽  
Genome Integrity ◽  
Chromatin States ◽  
Structural Framework ◽  
Cell Extracts ◽  
Dna Replication And Repair ◽  
Assembly Factor ◽  
Ordered Assembly

Chromatin is no longer considered to be a static structural framework for packaging DNA within the nucleus but is instead believed to be an interactive component of DNA metabolism. The ordered assembly of chromatin produces a nucleoprotein template capable of epigenetically regulating the expression and maintenance of the genome. Factors have been isolated from cell extracts that stimulate early steps in chromatin assembly in vitro. The function of one such factor, chromatin-assembly factor 1 (CAF-1), might extend beyond simply facilitating the progression through an individual assembly reaction to its active participation in a marking system. This marking system could be exploited at the crossroads of DNA replication and repair to monitor genome integrity and to define particular epigenetic states.

Succinylation at a key residue of FEN1 is involved in the DNA damage response to maintain genome stability

2020 ◽  
Vol 319 (4) ◽  
pp. C657-C666
Author(s):  
Rongyi Shi ◽  
Yiyi Wang ◽  
Ya Gao ◽  
Xiaoli Xu ◽  
Shuyu Mao ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Replication Fork ◽  
Genome Stability ◽  
Damage Response ◽  
Dna Replication And Repair ◽  
Fork Stalling ◽  
Stalled Replication Forks ◽  
Maintain Genome Stability

Human flap endonuclease 1 (FEN1) is a structure-specific, multifunctional endonuclease essential for DNA replication and repair. Our previous study showed that in response to DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of PCNA to engage in DNA repair activities, such as stalled DNA replication fork repair, and undergoes SUMOylation by SUMO-1. Here, we report that succinylation of FEN1 was stimulated in response to DNA replication fork-stalling agents, such as ultraviolet (UV) irradiation, hydroxyurea, camptothecin, and mitomycin C. K200 is a key succinylation site of FEN1 that is essential for gap endonuclease activity and could be suppressed by methylation and stimulated by phosphorylation to promote SUMO-1 modification. Succinylation at K200 of FEN1 promoted the interaction of FEN1 with the Rad9-Rad1-Hus1 complex to rescue stalled replication forks. Impairment of FEN1 succinylation led to the accumulation of DNA damage and heightened sensitivity to fork-stalling agents. Altogether, our findings suggest an important role of FEN1 succinylation in regulating its roles in DNA replication and repair, thus maintaining genome stability.

scholarly journals Bromodomain proteins: protectors against endogenous DNA damage and facilitators of genome integrity

2021 ◽  
Author(s):  
Seo Yun Lee ◽  
Jae Jin Kim ◽  
Kyle M. Miller
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Stress Responses ◽  
Genome Stability ◽  
Cancer Development ◽  
Genome Integrity ◽  
Major Contributor ◽  
Damage Response ◽  
Bromodomain Proteins

AbstractEndogenous DNA damage is a major contributor to mutations, which are drivers of cancer development. Bromodomain (BRD) proteins are well-established participants in chromatin-based DNA damage response (DDR) pathways, which maintain genome integrity from cell-intrinsic and extrinsic DNA-damaging sources. BRD proteins are most well-studied as regulators of transcription, but emerging evidence has revealed their importance in other DNA-templated processes, including DNA repair and replication. How BRD proteins mechanistically protect cells from endogenous DNA damage through their participation in these pathways remains an active area of investigation. Here, we review several recent studies establishing BRD proteins as key influencers of endogenous DNA damage, including DNA–RNA hybrid (R-loops) formation during transcription and participation in replication stress responses. As endogenous DNA damage is known to contribute to several human diseases, including neurodegeneration, immunodeficiencies, cancer, and aging, the ability of BRD proteins to suppress DNA damage and mutations is likely to provide new insights into the involvement of BRD proteins in these diseases. Although many studies have focused on BRD proteins in transcription, evidence indicates that BRD proteins have emergent functions in DNA repair and genome stability and are participants in the etiology and treatment of diseases involving endogenous DNA damage.

scholarly journals More than Meets the ISG15: Emerging Roles in the DNA Damage Response and Beyond

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1557
Author(s):  
Zac Sandy ◽  
Isabelle Cristine da Costa ◽  
Christine K. Schmidt
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Genome Stability ◽  
Post Translational Modifications ◽  
Free Dna ◽  
Damage Response ◽  
Dna Replication And Repair ◽  
Health And Disease ◽  
Interferon Stimulated Gene 15

Maintenance of genome stability is a crucial priority for any organism. To meet this priority, robust signalling networks exist to facilitate error-free DNA replication and repair. These signalling cascades are subject to various regulatory post-translational modifications that range from simple additions of chemical moieties to the conjugation of ubiquitin-like proteins (UBLs). Interferon Stimulated Gene 15 (ISG15) is one such UBL. While classically thought of as a component of antiviral immunity, ISG15 has recently emerged as a regulator of genome stability, with key roles in the DNA damage response (DDR) to modulate p53 signalling and error-free DNA replication. Additional proteomic analyses and cancer-focused studies hint at wider-reaching, uncharacterised functions for ISG15 in genome stability. We review these recent discoveries and highlight future perspectives to increase our understanding of this multifaceted UBL in health and disease.

scholarly journals Hypusination, a Metabolic Posttranslational Modification of eIF5A in Plants during Development and Environmental Stress Responses

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1261
Author(s):  
Péter Pálfi ◽  
László Bakacsy ◽  
Henrietta Kovács ◽  
Ágnes Szepesi
Keyword(s):  
Amino Acid ◽  
Environmental Stress ◽  
Plant Development ◽  
Stress Responses ◽  
Posttranslational Modification ◽  
Proper Function ◽  
Signal Pathways ◽  
Deoxyhypusine Synthase ◽  
Deoxyhypusine Hydroxylase ◽  
Eukaryotic Translation

Hypusination is a unique posttranslational modification of eIF5A, a eukaryotic translation factor. Hypusine is a rare amino acid synthesized in this process and is mediated by two enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Despite the essential participation of this conserved eIF5A protein in plant development and stress responses, our knowledge of its proper function is limited. In this review, we demonstrate the main findings regarding how eIF5A and hypusination could contribute to plant-specific responses in growth and stress-related processes. Our aim is to briefly discuss the plant-specific details of hypusination and decipher those signal pathways which can be effectively modified by this process. The diverse functions of eIF5A isoforms are also discussed in this review.

scholarly journals The Amazing Acrobat: Yeast’s Histone H3K56 Juggles Several Important Roles While Maintaining Perfect Balance

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 342
Author(s):  
Lihi Gershon ◽  
Martin Kupiec
Keyword(s):  
Dna Replication ◽  
Genome Stability ◽  
Entry And Exit ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes ◽  
M Phase ◽  
Dna Replication And Repair ◽  
H3k56 Acetylation ◽  
Timely Fashion ◽  
The Many

Acetylation on lysine 56 of histone H3 of the yeast Saccharomyces cerevisiae has been implicated in many cellular processes that affect genome stability. Despite being the object of much research, the complete scope of the roles played by K56 acetylation is not fully understood even today. The acetylation is put in place at the S-phase of the cell cycle, in order to flag newly synthesized histones that are incorporated during DNA replication. The signal is removed by two redundant deacetylases, Hst3 and Hst4, at the entry to G2/M phase. Its crucial location, at the entry and exit points of the DNA into and out of the nucleosome, makes this a central modification, and dictates that if acetylation and deacetylation are not well concerted and executed in a timely fashion, severe genomic instability arises. In this review, we explore the wealth of information available on the many roles played by H3K56 acetylation and the deacetylases Hst3 and Hst4 in DNA replication and repair.

scholarly journals A Tale of Ice and Fire: The Dual Role for 17β-Estradiol in Balancing DNA Damage and Genome Integrity

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1583
Author(s):  
Sara Pescatori ◽  
Francesco Berardinelli ◽  
Jacopo Albanesi ◽  
Paolo Ascenzi ◽  
Maria Marino ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cellular Transformation ◽  
Genome Integrity ◽  
Physiological Effects ◽  
Dna Damages ◽  
Cellular Effects ◽  
Damage Response ◽  
17Β Estradiol ◽  
Cellular Pathways ◽  
Definition Of

17β-estradiol (E2) regulates human physiology both in females and in males. At the same time, E2 acts as a genotoxic substance as it could induce DNA damages, causing the initiation of cellular transformation. Indeed, increased E2 plasma levels are a risk factor for the development of several types of cancers including breast cancer. This paradoxical identity of E2 undermines the foundations of the physiological definition of “hormone” as E2 works both as a homeostatic regulator of body functions and as a genotoxic compound. Here, (i) the molecular circuitries underlying this double face of E2 are reviewed, and (ii) a possible framework to reconcile the intrinsic discrepancies of the E2 function is reported. Indeed, E2 is a regulator of the DNA damage response, which this hormone exploits to calibrate its genotoxicity with its physiological effects. Accordingly, the genes required to maintain genome integrity belong to the E2-controlled cellular signaling network and are essential for the appearance of the E2-induced cellular effects. This concept requires an “upgrade” to the vision of E2 as a “genotoxic hormone”, which balances physiological and detrimental pathways to guarantee human body homeostasis. Deregulation of this equilibrium between cellular pathways would determine the E2 pathological effects.

Sign in / Sign up

Export Citation Format

Share Document