scholarly journals DNA translocation mechanism of an XPD family helicase

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kaiying Cheng ◽  
Dale B Wigley
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Genome Stability ◽  
Family Members ◽  
Dna Lesions ◽  
Human Diseases ◽  
Dna Translocation ◽  
Conserved Residues ◽  
Translocation Mechanism ◽  
Bulky Dna Lesions

The XPD family of helicases, that includes human disease-related FANCJ, DDX11 and RTEL1, are Superfamily two helicases that contain an iron-sulphur cluster domain, translocate on ssDNA in a 5’−3’ direction and play important roles in genome stability. Consequently, mutations in several of these family members in eukaryotes cause human diseases. Family members in bacteria, such as the DinG helicase from Escherichia coli, are also involved in DNA repair. Here we present crystal structures of complexes of DinG bound to single-stranded DNA (ssDNA) in the presence and absence of an ATP analogue (ADP•BeF3), that suggest a mechanism for 5’−3’ translocation along the ssDNA substrate. This proposed mechanism has implications for how those enzymes of the XPD family that recognise bulky DNA lesions might stall at these as the first step in initiating DNA repair. Biochemical data reveal roles for conserved residues that are mutated in human diseases.

scholarly journals DNA–protein crosslink proteases in genome stability

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Annamaria Ruggiano ◽  
Kristijan Ramadan
Keyword(s):  
Dna Replication ◽  
Cancer Therapy ◽  
Genome Stability ◽  
Dna Lesions ◽  
Protein Component ◽  
Human Diseases ◽  
Direct Link ◽  
The Past ◽  
Protein Crosslinks ◽  
Bulky Dna Lesions

AbstractProteins covalently attached to DNA, also known as DNA–protein crosslinks (DPCs), are common and bulky DNA lesions that interfere with DNA replication, repair, transcription and recombination. Research in the past several years indicates that cells possess dedicated enzymes, known as DPC proteases, which digest the protein component of a DPC. Interestingly, DPC proteases also play a role in proteolysis beside DPC repair, such as in degrading excess histones during DNA replication or controlling DNA replication checkpoints. Here, we discuss the importance of DPC proteases in DNA replication, genome stability and their direct link to human diseases and cancer therapy.

scholarly journals Overview of DNA Repair inTrypanosoma cruzi, Trypanosoma brucei,andLeishmania major

2010 ◽  
Vol 2010 ◽  
pp. 1-14 ◽  
Author(s):  
Danielle Gomes Passos-Silva ◽  
Matheus Andrade Rajão ◽  
Pedro Henrique Nascimento de Aguiar ◽  
João Pedro Vieira-da-Rocha ◽  
Carlos Renato Machado ◽  
...  
Keyword(s):  
Dna Repair ◽  
Trypanosoma Brucei ◽  
Genome Stability ◽  
Leishmania Major ◽  
Experimental Studies ◽  
Life Cycles ◽  
Dna Lesions ◽  
Cellular Mechanisms ◽  
Environmental Agents ◽  
Maintain Genome Stability

A wide variety of DNA lesions arise due to environmental agents, normal cellular metabolism, or intrinsic weaknesses in the chemical bonds of DNA. Diverse cellular mechanisms have evolved to maintain genome stability, including mechanisms to repair damaged DNA, to avoid the incorporation of modified nucleotides, and to tolerate lesions (translesion synthesis). Studies of the mechanisms related to DNA metabolism in trypanosomatids have been very limited. Together with recent experimental studies, the genome sequencing ofTrypanosoma brucei, Trypanosoma cruzi,andLeishmania major, three related pathogens with different life cycles and disease pathology, has revealed interesting features of the DNA repair mechanism in these protozoan parasites, which will be reviewed here.

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.

scholarly journals A gatekeeping function of the replicative polymerase controls pathway choice in the resolution of lesion-stalled replisomes

2019 ◽  
Vol 116 (51) ◽  
pp. 25591-25601 ◽  
Author(s):  
Seungwoo Chang ◽  
Karel Naiman ◽  
Elizabeth S. Thrall ◽  
James E. Kath ◽  
Slobodan Jergic ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Synthesis ◽  
Genome Stability ◽  
Structural Changes ◽  
Translesion Synthesis ◽  
Dynamic Interaction ◽  
Dna Lesions ◽  
Exonuclease Activity ◽  
Replication Fidelity ◽  
Proper Resolution

DNA lesions stall the replisome and proper resolution of these obstructions is critical for genome stability. Replisomes can directly replicate past a lesion by error-prone translesion synthesis. Alternatively, replisomes can reprime DNA synthesis downstream of the lesion, creating a single-stranded DNA gap that is repaired primarily in an error-free, homology-directed manner. Here we demonstrate how structural changes within theEscherichia colireplisome determine the resolution pathway of lesion-stalled replisomes. This pathway selection is controlled by a dynamic interaction between the proofreading subunit of the replicative polymerase and the processivity clamp, which sets a kinetic barrier to restrict access of translesion synthesis (TLS) polymerases to the primer/template junction. Failure of TLS polymerases to overcome this barrier leads to repriming, which competes kinetically with TLS. Our results demonstrate that independent of its exonuclease activity, the proofreading subunit of the replisome acts as a gatekeeper and influences replication fidelity during the resolution of lesion-stalled replisomes.

scholarly journals SbcCD Regulation and Localization in Escherichia coli

2007 ◽  
Vol 189 (18) ◽  
pp. 6686-6694 ◽  
Author(s):  
Elise Darmon ◽  
Manuel A. Lopez-Vernaza ◽  
Anne C. Helness ◽  
Amanda Borking ◽  
Emily Wilson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Dna Repair ◽  
Genome Stability ◽  
Cellular Localization ◽  
Replication Factory

ABSTRACTThe SbcCD complex and its homologues play important roles in DNA repair and in the maintenance of genome stability. InEscherichia coli, the in vitro functions of SbcCD have been well characterized, but its exact cellular role remains elusive. This work investigates the regulation of thesbcDCoperon and the cellular localization of the SbcC and SbcD proteins. Transcription of thesbcDCoperon is shown to be dependent on starvation and RpoS protein. Overexpressed SbcC protein forms foci that colocalize with the replication factory, while overexpressed SbcD protein is distributed through the cytoplasm.

scholarly journals Tyrosyl-DNA Phosphodiesterase I N-Terminal Domain Modifications and Interactions Regulate Cellular Function

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 897 ◽  
Author(s):  
Brettrager ◽  
Segura ◽  
van Waardenburg
Keyword(s):  
Dna Repair ◽  
Dna Adducts ◽  
Protein Interactions ◽  
Genome Stability ◽  
Cellular Localization ◽  
Genome Instability ◽  
Dna Lesions ◽  
Reaction Products ◽  
Protein Levels ◽  
Terminal Domain

The conserved eukaryotic DNA repair enzyme Tyrosyl-DNA phosphodiesterase I (Tdp1) removes a diverse array of adducts from the end of DNA strand breaks. Tdp1 specifically catalyzes the hydrolysis of phosphodiester linked DNA-adducts. These DNA lesions range from damaged nucleotides to peptide-DNA adducts to protein-DNA covalent complexes and are products of endogenously or exogenously induced insults or simply failed reaction products. These adducts include DNA inserted ribonucleotides and non-conventional nucleotides, as well as covalent reaction intermediates of DNA topoisomerases with DNA and a Tdp1-DNA adduct in trans. This implies that Tdp1 plays a role in maintaining genome stability and cellular homeostasis. Dysregulation of Tdp1 protein levels or catalysis shifts the equilibrium to genome instability and is associated with driving human pathologies such as cancer and neurodegeneration. In this review, we highlight the function of the N-terminal domain of Tdp1. This domain is understudied, structurally unresolved, and the least conserved in amino acid sequence and length compared to the rest of the enzyme. However, over time it emerged that the N-terminal domain was post-translationally modified by, among others, phosphorylation, SUMOylation, and Ubiquitinoylation, which regulate Tdp1 protein interactions with other DNA repair associated proteins, cellular localization, and Tdp1 protein stability.

scholarly journals Detection of bulky DNA lesions: DDB2 at the interface of chromatin and DNA repair in eukaryotes

IUBMB Life ◽  
2010 ◽  
Vol 62 (11) ◽  
pp. 803-811 ◽  
Author(s):  
Kristi L. Jones ◽  
Ling Zhang ◽  
Kenneth L. Seldeen ◽  
Feng Gong
Keyword(s):  
Dna Repair ◽  
Dna Lesions ◽  
Bulky Dna Lesions

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.

Role of the two ATPase domains of Escherichia coli UvrA in binding non-bulky DNA lesions and interaction with UvrB

DNA Repair ◽  
2010 ◽  
Vol 9 (11) ◽  
pp. 1176-1186 ◽  
Author(s):  
Koen Wagner ◽  
Geri F. Moolenaar ◽  
Nora Goosen
Keyword(s):  
Escherichia Coli ◽  
Dna Lesions ◽  
Bulky Dna Lesions

scholarly journals Emerging roles of RNA modifications in genome integrity

2020 ◽  
Author(s):  
Seo Yun Lee ◽  
Jae Jin Kim ◽  
Kyle M Miller
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
Genome Stability ◽  
Strand Break ◽  
Human Diseases ◽  
Genome Integrity ◽  
Rna Modification ◽  
Rna Modifications ◽  
Dna Double Strand Break

Abstract Post-translational modifications of proteins are well-established participants in DNA damage response (DDR) pathways, which function in the maintenance of genome integrity. Emerging evidence is starting to reveal the involvement of modifications on RNA in the DDR. RNA modifications are known regulators of gene expression but how and if they participate in DNA repair and genome maintenance has been poorly understood. Here, we review several studies that have now established RNA modifications as key components of DNA damage responses. RNA modifying enzymes and the binding proteins that recognize these modifications localize to and participate in the repair of UV-induced and DNA double-strand break lesions. RNA modifications have a profound effect on DNA–RNA hybrids (R-loops) at DNA damage sites, a structure known to be involved in DNA repair and genome stability. Given the importance of the DDR in suppressing mutations and human diseases such as neurodegeneration, immunodeficiencies, cancer and aging, RNA modification pathways may be involved in human diseases not solely through their roles in gene expression but also by their ability to impact DNA repair and genome stability.

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