Alkylated DNA repair by a novel HhH-GPD family protein from Crenarchaea.

HhH-GPD (helix-hairpin-helix-glycine/proline/aspartate) family proteins are involved in DNA damage repair. Currently, mechanism of alkylated DNA repair in Crenarchaea has not been fully clarified. The hyperthermophilic model crenarchaeon Saccharolobus islandicus REY15A possesses a novel HhH-GPD family protein (Sis-HhH-GPD), where its Ser152 corresponds to a conserved catalytic Asp in other HhH-GPD homologs.

Cobalt-Catalyzed Intramolecular Markovnikov Hydrocarbonylation of Unactivated Alkenes via Hydrogen Atom Transfer.

A cobalt-catalyzed intramolecular Markovnikov hydroalkoxycarbonylation and hydroaminocarbonylation of unactivated alkenes has been developed, enabling highly chemo- and regioselective synthesis of α-alkylated γ-lactones and α-alkylated γ-lactams in good yields. The mild reaction conditions allow use of mono-, di- and trisubstituted alkenes bearing a variety of functional groups. Preliminary mechanistic studies suggest the reaction proceeds through a CO-mediated hydrogen atom transfer (HAT) and radical-polar crossover (RPC) process, in which a cationic acylcobalt(IV) complex is proposed as the key intermediate.

The RPA-RNF20-SNF2H cascade promotes proper chromosome segregation and homologous recombination repair.

The human tumor suppressor Ring finger protein 20 (RNF20)-mediated histone H2B monoubiquitination (H2Bub) is essential for proper chromosome segregation and DNA repair. However, what is the precise function and mechanism of RNF20-H2Bub in chromosome segregation and how this pathway is activated to preserve genome stability remain unknown. Here, we show that the single-strand DNA-binding factor Replication protein A (RPA) interacts with RNF20 mainly in the S and G2/M phases and recruits RNF20 to mitotic centromeres in a centromeric R-loop-dependent manner.

Proper RPA acetylation promotes accurate DNA replication and repair.

The single-stranded DNA (ssDNA) binding protein complex RPA plays a critical role in promoting DNA replication and multiple DNA repair pathways. However, how RPA is regulated to achieve its functions precisely in these processes remains elusive. Here, we found that proper acetylation and deacetylation of RPA are required to regulate RPA function in promoting high-fidelity DNA replication and repair.

Biochemical and functional characterization of an endonuclease III from Thermococcus barophilus Ch5.

Endonuclease III (EndoIII) is a bifunctional DNA glycosylase that is essential to excise thymine glycol (Tg) from DNA. Although EndoIII is widespread in bacteria, eukarya and Archaea, our understanding on archaeal EndoIII function remains relatively incomplete due to the limited reports. Herein, we characterized an EndoIII from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tba-EndoIII) biochemically, demonstrating that the enzyme can excise Tg from dsDNA and display maximum activity at 50 ~ 70 °C and at pH 6.

A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophilus Ch5 is a new member of AGOG DNA glycosylase family.

8-Oxoguanine (8oxoG) in DNA is a major oxidized base that poses a severe threat to genome stability. To counteract the mutagenic effect generated by 8oxoG in DNA, cells have evolved 8oxoG DNA glycosylase (OGG) that can excise this oxidized base from DNA. Currently, OGG enzymes have been divided into three families: OGG1, OGG2 and AGOG (archaeal 8oxoG DNA glycosylase).

Biochemical characterization and mutational analysis of a novel flap endonuclease 1 from Thermococcus barophilus Ch5.

Flap endonuclease 1 (FEN1) plays important roles in DNA replication, repair and recombination. Herein, we report biochemical characteristics and catalytic mechanism of a novel FEN1 from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tb-FEN1). As expected, the recombinant Tb-FEN1 can cleave 5'-flap DNA.

Biochemical characterization and mutational studies of a thermostable endonuclease III from Sulfolobus islandicus REY15A.

Endonuclease III (EndoIII), which is ubiquitous in bacteria, Archaea and eukaryotes, plays an important role in excising thymine glycol (Tg) from DNA. Herein, we present evidence that an EndoIII from the hyperthermophilic crenarchaeon Sulfolobus islandicus REY15A (Sis-EndoIII) is capable of removing Tg from DNA at high temperature. Biochemical data show that the optimal temperature and pH of Sis-EndoIII are ca.

Discovery of novel chromone derivatives containing a sulfonamide moiety as potential anti-TSWV agents.

A number of chromone derivatives containing sulfonamide structure were designed and synthesized. Firstly, the target compounds were evaluated for anti-TSWV activities in vivo by the half-leaf method. We found that most of the compounds had good anti-TSWV activities.

Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method.

A number of novel chromone derivatives containing sulfonamide moieties were designed and synthesized, and the activity of compounds against tomato chlorosis virus (ToCV) was assessed using the ToCVCP-oriented screening method. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were established based on the dissociation constant () values of the target compounds, and compound was designed and synthesized with the aid of CoMFA and CoMSIA models. The study of affinity interaction indicated that compound exhibited excellent affinity with ToCVCP with a value of 0.

Repair of Hypoxanthine in DNA Revealed by DNA Glycosylases and Endonucleases From Hyperthermophilic Archaea.

Since hyperthermophilic Archaea (HA) thrive in high-temperature environments, which accelerate the rates of deamination of base in DNA, their genomic stability is facing a severe challenge. Hypoxanthine (Hx) is one of the common deaminated bases in DNA. Generally, replication of Hx in DNA before repaired causes AT → GC mutation.

Identification of a novel bifunctional uracil DNA glycosylase from Thermococcus barophilus Ch5.

Genomes of hyperthermophiles are facing a severe challenge due to increased deamination rates of cytosine induced by high temperature, which could be counteracted by base excision repair mediated by uracil DNA glycosylase (UDG) or other repair pathways. Our previous work has shown that the two UDGs (Tba UDG247 and Tba UDG194) encoded by the genome of the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 can remove uracil from DNA at high temperature. Herein, we provide evidence that Tba UDG247 is a novel bifunctional glycosylase which can excise uracil from DNA and further cleave the phosphodiester bo nd of the generated apurinic/apyrimidinic (AP) site, which has never been described to date.

Characterization of a novel type III alcohol dehydrogenase from Thermococcus barophilus Ch5.

The genome of the hyperthermophilic and piezophilic euryarchaeaon Thermococcus barophilus Ch5 encodes three putative alcohol dehydrogenases (Tba ADHs). Herein, we characterized Tba ADH biochemically and probed its catalytic mechanism by mutational studies. Our data demonstrate that Tba ADH can oxidize ethanol and reduce acetaldehyde at high temperature with the same optimal temperature (75 °C) and exhibit similar thermostability for oxidization and reduction reactions.

Biochemical characterization and mutational studies of a novel 3-methlyadenine DNA glycosylase II from the hyperthermophilic Thermococcus gammatolerans.

The hyperthermophilic and radioresistant euryarchaeon Thermococcus gammatolerans encodes a putative 3-methlyadenine DNA glycosylase II (Tg-AlkA). Herein, we report biochemical characterization and catalytic mechanism of Tg-AlkA. The recombinant Tg-AlkA can excise hypoxanthine (Hx) and 1-methlyadenine (1-meA) from dsDNA with varied efficiencies at high temperature.

Design, Synthesis, Antiviral Bioactivity, and Mechanism of the Ferulic Acid Ester-Containing Sulfonamide Moiety.

Tobacco mosaic virus (TMV) has caused huge economic losses to tobacco, pepper, cucumber, and ornamental crops all over the world. However, few effective antiviral agents were developed and applied to control such plant disease. It is challenging to find an anti-TMV agent which is highly effective, less toxic, and environmentally friendly.

New Insights Into DNA Repair Revealed by NucS Endonucleases From Hyperthermophilic Archaea.

Hyperthermophilic Archaea (HA) thrive in high temperature environments and their genome is facing severe stability challenge due to the increased DNA damage levels caused by high temperature. Surprisingly, HA display spontaneous mutation frequencies similar to mesophilic microorganisms, thereby indicating that the former must possess more efficient DNA repair systems than the latter to counteract the potentially enhanced mutation rates under the harsher environment. Although a few repair proteins or enzymes from HA have been biochemically and structurally characterized, the molecular mechanisms of DNA repair of HA remain largely unknown.

Design, Synthesis, and Anti-ToCV Activity of Novel Pyrimidine Derivatives Bearing a Dithioacetal Moiety that Targets ToCV Coat Protein.

Novel pyrimidine sulfide derivatives containing a dithioacetal and strobilurin moiety were designed and synthesized. Their antiviral activities against tomato chlorosis virus (ToCV) were investigated through the tomato chlorosis virus coat protein (ToCVCP)-oriented screening method. Microscale thermophoresis was used to study the interaction between the compound and the ToCVCP.

Characterization and application of a family B DNA polymerase from the hyperthermophilic and radioresistant euryarchaeon Thermococcus gammatolerans.

Thermococcus gammatolerans is anaerobic euryarchaeon which grows optimally at 88 °C and its genome encodes a family B DNA polymerase (Tga PolB). Herein, we cloned the gene of Tga PolB, expressed and purified the gene product, and characterized the enzyme biochemically. The recombinant Tga PolB can efficiently synthesize DNA at high temperature, and retain 93% activity after heated at 95 °C for 1.

Design, synthesis and anti-TMV activities of novel chromone derivatives containing dithioacetal moiety.

Thirty-five novel chromone derivatives containing dithioacetal moiety were designed, synthesized, and their anti-TMV activities were evaluated through half-leaf method. The results showed compound c23 illustrates highly curative, protective and inactivating activities against TMV at 500 mg/L, with the values of 68.8%, 58.

Biochemical characterization and mutational studies of a thermostable uracil DNA glycosylase from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5.

Uracil DNA glycosylases (UDGs) play an important role in removing uracil from DNA to initiate DNA base excision repair. Here, we characterized biochemically a thermostable UDG from the hyperthermophilic euryarchaeon Thermococcus barophilus Ch5 (Tba UDG), and probed its mechanism by mutational analysis. The recombinant Tba UDG cleaves exclusively uracil-containing ssDNA and dsDNA at 65°C.

A comparative study of CH adsorption properties in five isomeric copper-based MOFs based on naphthalene-derived diisophthalates.

In this work, five positional isomeric ligands consisting of two peripheral isophthalate moieties attached to the central naphthyl core in different ways, namely, 5,5'-(naphthyl-1,3-diyl) diisophthalate (HL1), 5,5'-(naphthyl-1,4-diyl) diisophthalate (HL2), 5,5'-(naphthyl-1,5-diyl) diisophthalate (HL3), 5,5'-(naphthyl-1,6-diyl) diisophthalate (HL4) and 5,5'-(naphthyl-2,6-diyl) diisophthalate (HL5), have been used to generate five copper-based MOF isomers. As revealed by single-crystal X-ray diffraction studies, they adopted two different types of topologies depending on the organic ligands: ssa topology for the MOFs ZJNU-71 and ZJNU-74 based on the ligands HL1 and HL4, respectively, and nbo topology for the MOFs ZJNU-72, ZJNU-73 and NOTT-103 derived from the ligands HL2, HL3 and HL5, respectively. Furthermore, their CH adsorption properties were systematically investigated, revealing that their different CH uptake capacities can be mainly related to their different pore sizes since they possess the same chemical compositions and gravimetric densities of open metal sites.

A porous metal-organic framework based on an asymmetric angular diisophthalate for selective adsorption of CH and CO over CH.

A new copper-based metal-organic framework [CuL(HO)]·5DMF·2HO (ZJNU-56) has been solvothermally synthesized using a custom-designed asymmetric rigid bent diisophthalate ligand, 5,5'-(1-amine-naphthyl-2,4-diyl) diisophthalic acid (HL), and structurally determined by single-crystal X-ray diffraction. ZJNU-56 features a three-dimensional (3D) open framework incorporating three different types of metal-organic cages and two distinct types of one-dimensional channels. With a moderate BET surface area of 1655 m g, optimized pore structure, and functional sites (open copper sites and Lewis basic amine groups) on the cage surface, ZJNU-56 after desolvation exhibits highly selectively adsorptive separation of CH and CO over CH under ambient conditions.