Activity

While many labs have made significant contributions to our understanding of Pol β, the focus of this article is on the long history of the contributions from the Wilson lab. We have chosen to highlight select seminal Pol β structures with emphasis on the overarching contributions each structure has made to the field.Canonical DNA mismatch repair (MMR) excises base-base mismatches to increase the fidelity of DNA replication. Thus, loss of MMR leads to increased spontaneous mutagenesis. MMR genes also are involved in the suppression of mutagenic, and the induction of protective, responses to various types of DNA damage. In this review we describe these non-canonical roles of MMR at different lesion types. Loss of non-canonical MMR gene functions may have important ramifications for the prevention, development and treatment of colorectal cancer associated with inherited MMR gene defects in Lynch syndrome. This graphical review pays tribute to Samuel H. Wilson. Sam not only made seminal contributions to understanding base excision repair, particularly with respect to structure-function relationships in DNA polymerase β but also, as Editor of DNA Repair, has maintained a high standard of the journal.Base excision repair (BER) addresses the numerous base lesions and strand breaks induced by exogenous and endogenous stressors daily. The complexity and importance of BER requires careful regulation of basal levels of these proteins and inducible responses following DNA damage. Several reports have noted the dysregulation of BER proteins and defects in BER capacity in cancer. Modulated gene and protein expression of several BER proteins, including APE1, PARP1, POL β, and XRCC1, have been observed in breast cancer. Overexpression of these factors has been associated with chemoresistance and cancer aggressiveness, but the regulatory mechanisms that drive overexpression have not been defined. Here, we review the known transcriptional regulators of these key BER proteins and examine potential mechanisms that may drive overexpression in breast cancer.Damage to DNA bases occurs continuously in cells as a result of the intrinsic instability of nucleic acids and because of the presence of intracellular and environmental genotoxins. As a consequence, all living cells possess a highly conserved biochemical pathway by which damaged DNA bases are detected, removed, and replaced with undamaged bases. This pathway is denoted DNA base excision repair (BER) and is critical for genome stability and human health. Selleck Pentylenetetrazol In this review I summarise the key features of mammalian BER, highlighting both the molecular choreography that coordinates this pathway and its importance for human health.DNA mismatch repair (MMR) maintains genomic stability primarily by correcting replication errors. Defects in MMR lead to cancers and cause resistance to many chemotherapeutic drugs. Emerging evidence reveals that MMR is coupled with replication and precisely regulated in the context of chromatin; strikingly, tumors defective in MMR are highly responsive to immune checkpoint blockade therapy. As a tribute to Dr. Samuel Wilson for his many scientific contributions to the field of DNA repair and his leadership as Editor-in-Chief of the journal DNA Repair, we summarize recent developments in research on MMR at the chromatin level, its implications for tumorigenesis, and its therapeutic potential.Mammalian cells possess multiple closely related SWI/SNF chromatin remodelling complexes. These complexes have been implicated in the cellular response to DNA double strand breaks (DSBs). Evidence suggests that SWI/SNF complexes contribute to successful repair via both the homologous recombination and non-homologous end joining pathways. In addition, repressing transcription near DSBs is dependent on SWI/SNF activity. Understanding these roles is important because SWI/SNF complexes are frequently dysregulated in cancer, and DNA DSB repair defects have the potential to be therapeutically exploited. In this graphical review, we summarise what is known about SWI/SNF contribution to DNA DSB responses in mammalian cells and provide an overview of the SWI/SNF-encoding gene alteration spectrum in human cancers.Nanoparticles (NPs) sink into the soil via agricultural spreading, surface water, atmospheric deposition, and industrial emission, which affects plant growth and soil microenvironment. To understand how NPs influence urban soil microenvironment, the effect of typical nano-pollutants zinc oxide nanoparticles (ZnONPs) was investigated in urban solid-waste land. Pokeweed (Phytolacca Americana L.) soil samples from solid-waste land were collected and exposed to 200, 500, and 1000 mg kg-1 ZnONPs. The physiological characteristics of pokeweed, soil bacterial community composition, and soil physiochemical properties and enzymatic activities were determined. Our results show that pokeweed growth was slightly inhibited, and soil acid-base homeostasis was affected in ZnONPs-contaminated samples. Meanwhile, enzymatic activities related to soil C cycle were enhanced, and bacterial community structure at the phylum and genus levels was altered. Specifically, the abundance of hydrocarbon-degrading taxa reduced substantially upon ZnONPs exposure. The phenoloxidase (PPO) activity and the refractory hydrocarbon-degrading bacteria Bacteroidetes was adversely affected by ZnONPs exposure. In addition, Subgroup_10 of Acidobacteria was identified as an indicator of soil ZnONPs contamination. Our study detected changes in plant growth, soil environmental factors, and soil microbe community composition in urban solid-waste land treated by ZnONPs. The results of this research provide evidence for ZnONPs toxicology on urban soil microenvironment.Nickel-based metal-organic framework (Ni-MOF) was employed as a sacrificial template for the preparation of nickel-cobalt layered double hydroxide (NiCo-LDH) under different hydrolysis time. The template etching rate varied at different hydrolysis time, resulting in variations of the structural and morphology of NiCo-LDHs. The NiCo-LDH/10 sample showed a large specific surface area and the well-oriented larger dimension of thinner sheets due to the sufficient in-situ etching of the Ni-MOF template. The NiCo-LDH/10 was an excellent heterogeneous catalyst to activate peroxymonosulfate (PMS) for highly efficient Reactive Red-120 dye degradation. The results exhibited that the degradation efficiency of the NiCo-LDH/10-PMS catalyst was 89% for RR-120 dye within 10 min in the presence of the PMS system, which is higher than other NiCo-LDHs. Moreover, the other influencing factors such as PMS concentration, catalyst dosage, initial pH were also investigated towards degradation. The radical quenching measurement proved that the sulfate (SO4•-) and hydroxyl (OH•) had been indicated as the primary radicals.