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The year 2023 was the warmest year since 1850. Greenhouse gases, including CO2 and methane, played a significant role in increasing global warming. Among these gases, methane has a 25-fold greater impact on global warming than CO2. Methane is emitted during rice cultivation by a group of rice rhizosphere microbes, termed methanogens, in low oxygen (hypoxic) conditions. To reduce methane emissions, it is crucial to decrease the methane production capacity of methanogens through water and fertilizer management, breeding of new rice cultivars, regulating root exudation, and manipulating rhizosphere microbiota. In this opinion article we review the recent developments in hypoxia ecology and methane emission mitigation and propose potential solutions based on the manipulation of microbiota and methanogens for the mitigation of methane emissions.
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Wheat (Triticum aestivum L.) stands as a significant cereal crop globally, including in Korea, where its consumption reached 35.7 kg per capita in 2023. In the southern regions of Korea, wheat cultivation follows paddy rice, with harvesting typically occurring during the rainy season in mid-June. This timing, coupled with the high humidity and unpredictable rainfall, often leads to pre-harvest sprouting and subsequent deterioration in flour quality. To assess the impact of rain on flour quality, an artificial rain treatment was administered 45 days after heading in an open field greenhouse, followed by flour quality analysis. The color measurement revealed an increase in the L* parameter, indicative of enhanced kernel vitreousness, attributed to endosperm starch degradation via alpha-amylase activation induced by water absorption. Moreover, significant changes were observed in ash content and the gluten index within the wetted group, resulting in decreased dough strength and stability, ultimately leading to a reduction in loaf volume. Consequently, it is recommended that wheat be harvested 4-7 days after reaching the physiological maturity stage to avoid the rainy season and ensure the production of high-quality wheat.
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Wheat is a major food crop that plays a crucial role in the human diet. Various breeding technologies have been developed and refined to meet the increasing global wheat demand. Several studies have suggested breeding strategies that combine generation acceleration systems and molecular breeding methods to maximize breeding efficiency. However, real-world examples demonstrating the effective utilization of these strategies in breeding programs are lacking. In this study, we designed and demonstrated a synergized breeding strategy (SBS) that combines rapid and efficient breeding techniques, including speed breeding, speed vernalization, phenotypic selection, backcrossing, and marker-assisted selection. These breeding techniques were tailored to the specific characteristics of the breeding materials and objectives. Using the SBS approach, from artificial crossing to the initial observed yield trial under field conditions only took 3.5 years, resulting in a 53% reduction in the time required to develop a BC2 near-isogenic line (NIL) and achieving a higher recurrent genome recovery of 91.5% compared to traditional field conditions. We developed a new wheat NIL derived from cv. Jokyoung, a leading cultivar in Korea. Milyang56 exhibited improved protein content, sodium dodecyl sulfate-sedimentation value, and loaf volume compared to Jokyoung, which were attributed to introgression of the Glu-B1i allele from the donor parent, cv. Garnet. SBS represents a flexible breeding model that can be applied by breeders for developing breeding materials and mapping populations, as well as analyzing the environmental effects of specific genes or loci and for trait stacking.
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The Bloom syndrome (BLM) helicase is critical for alternative lengthening of telomeres (ALT), a homology-directed repair (HDR)-mediated telomere maintenance mechanism that is prevalent in cancers of mesenchymal origin. The DNA substrates that BLM engages to direct telomere recombination during ALT remain unknown. Here, we determine that BLM helicase acts on lagging strand telomere intermediates that occur specifically in ALT-positive cells to assemble a replication-associated DNA damage response. Loss of ATRX was permissive for BLM localization to ALT telomeres in S and G2, commensurate with the appearance of telomere C-strand-specific single-stranded DNA (ssDNA). DNA2 nuclease deficiency increased 5'-flap formation in a BLM-dependent manner, while telomere C-strand, but not G-strand, nicks promoted ALT. These findings define the seminal events in the ALT DNA damage response, linking aberrant telomeric lagging strand DNA replication with a BLM-directed HDR mechanism that sustains telomere length in a subset of human cancers.
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Daño del ADN , Replicación del ADN , RecQ Helicasas , Homeostasis del Telómero , Telómero , RecQ Helicasas/metabolismo , RecQ Helicasas/genética , Humanos , Telómero/metabolismo , Telómero/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/genética , Proteína Nuclear Ligada al Cromosoma X/genética , Proteína Nuclear Ligada al Cromosoma X/metabolismo , ADN Helicasas/metabolismo , ADN Helicasas/genética , Síndrome de Bloom/genética , Síndrome de Bloom/metabolismo , Síndrome de Bloom/enzimología , Síndrome de Bloom/patología , Línea Celular TumoralRESUMEN
OBJECTIVE: Emboli commonly occurs in mechanical thrombectomy (MT). The objective of this study was to analyze predicting factors of emboli after MT. METHODS: Patients who underwent MT with successful reperfusion for anterior circulation occlusion were enrolled. Emboli included distal emboli at digital subtraction angiography (DSA) and unexpected embolic infarct on diffusion-weighted image (DWI) without distal emboli at DSA. Baseline characteristics, procedural details, angiographic outcomes, and clinical outcomes were reviewed. Multivariable analyses were performed to evaluate predictive factors for the occurrence of emboli. RESULTS: Of 601 patients, 149 (24.8%) patients had distal emboli at DSA, and 169 (28.1%) patients had unexpected embolic infarction on DWI even without distal emboli at DSA. A total of 318 (52.9%) patients were enrolled in the embolic group, and 283 (47.1%) patients were assigned to the non-embolic group. In multivariate analysis, larger microcatheter (OR 1.26, 95% CI 1.12-1.94; p = 0.047), clot passage (OR 1.33, 95% CI 1.07-1.87; p = 0.041), use of balloon guide catheter (BGC) (OR 0.70, 95% CI 0.52-0.92; p = 0.014), early ballooning of BGC (OR 0.68, 95% CI 0.50-0.90; p = 0.009), and longer stent retriever (OR 0.72, 95% CI 0.54-0.90; p = 0.029) were associated with occurrence of emboli. CONCLUSION: MT with only a stent retriever, use of a larger microcatheter, and clot passage might increase the risk of emboli. In contrast, contact aspiration thrombectomy, use of BGC, early ballooning of BGC, and use of longer stent retrievers could reduce the chance of emboli.
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Fanconi anemia (FA) is characterized by congenital abnormalities, bone marrow failure, and cancer susceptibility. The central FA protein complex FANCI/FANCD2 (ID2) is activated by monoubiquitination and recruits DNA repair proteins for interstrand crosslink (ICL) repair and replication fork protection. Defects in the FA pathway lead to R-loop accumulation, which contributes to genomic instability. Here, we report that the splicing factor SRSF1 and FANCD2 interact physically and act together to suppress R-loop formation via mRNA export regulation. We show that SRSF1 stimulates FANCD2 monoubiquitination in an RNA-dependent fashion. In turn, FANCD2 monoubiquitination proves crucial for the assembly of the SRSF1-NXF1 nuclear export complex and mRNA export. Importantly, several SRSF1 cancer-associated mutants fail to interact with FANCD2, leading to inefficient FANCD2 monoubiquitination, decreased mRNA export, and R-loop accumulation. We propose a model wherein SRSF1 and FANCD2 interaction links DNA damage response to the avoidance of pathogenic R-loops via regulation of mRNA export.
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Anemia de Fanconi , Neoplasias , Humanos , Estructuras R-Loop , Transporte Activo de Núcleo Celular , Anemia de Fanconi/metabolismo , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/genética , Proteína del Grupo de Complementación D2 de la Anemia de Fanconi/metabolismo , Ubiquitinación , Reparación del ADN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Daño del ADN , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
This study employed a joint strategy high-density SNP Chip DNA markers and multiple Genome Association and Prediction Integrated Tool (GAPIT) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK), Fixed and random model Circulating Probability Uniform (FarmCPU), General Linear Model (GLM), and Settlement of Mixed Linear Model (MLM) Under Progressively Exclusive Relationship (SUPER)], to investigate novel genetic factors controlling mesocotyl elongation and seedling emergence for direct-seeded rice. Genotype data (230,526 SNP Chip DNA makers) of 117 doubled haploid lines (derived from a cross between 93-11 (Oryza sativa L. ssp. indica) and Milyang352 (O. sativa L. ssp. japonica) were used to perform a Genome-Wide Association Study (GWAS). Results revealed the association between five (5) topmost significant SNP markers, of which number two [AX-155741269, Chr2: 15422406 bp, and AX-155200917, Chr7: 23814085 bp, explaining 37.5% and 13.8% of the phenotypic variance explained (PVE)] are linked to the mesocotyl elongation loci, while three (AX-282097034 and AX-283652873, Chr9: 9882817 bp and 1023383 bp, PVE 64.5%, and 20.2%, respectively, and AX-154356231, Chr1: 17413989 bp, PVE 21.1%) are tightly linked to the loci controlling seedling emergence. The qMEL2-1 and qSEM9-1 are identified as major QTLs explaining 37.5% and 64.5% of the PVE for mesocotyl elongation and seedling emergence, respectively. The AX-282097034 (Chr9: 9882817 bp) was co-detected by four GAPIT models (BLINK, FarmCPU, SUPER, and GLM), while AX-155741269 was co-detected by BLINK and SUPER. Furthermore, a high estimated heritability (Mesocotyl elongation: h2 = 0.955; seedling emergence: h2 = 0.863; shoot length: h2 = 0.707) was observed. Genes harbored by qMEL2-1 and qSEM9-1 have interesting annotated molecular functions that could be investigated through functional studies to uncover their roles during mesocotyl elongation and seedling emergence events in rice. Furthermore, the presence of genes encoding transcription factors, growth- and stress response, or signaling-related genes would suggest that mesocotyl elongation and seedling emergence from deep direct-seeded rice might involve an active signaling cascade and transport of molecules, which could be elucidated through functional analysis. Likewise, genomic selection analysis suggested markers useful for downstream marker-assisted selection (MAS).
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This study investigated novel quantitative traits loci (QTLs) associated with the control of grain shape and size as well as grain weight in rice. We employed a joint-strategy multiple GAPIT (Genome Association and Prediction Integrated Tool) models [(Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK)), Fixed and random model Circulating Probability Uniform (FarmCPU), Settlement of MLM Under Progressive Exclusive Relationship (SUPER), and General Linear Model (GLM)]-High-Density SNP Chip DNA Markers (60,461) to conduct a Genome-Wide Association Study (GWAS). GWAS was performed using genotype and grain-related phenotypes of 143 recombinant inbred lines (RILs). Data show that parental lines (Ilpum and Tung Tin Wan Hein 1, TTWH1, Oryza sativa L., ssp. japonica and indica, respectively) exhibited divergent phenotypes for all analyzed grain traits), which was reflected in their derived population. GWAS results revealed the association between seven SNP Chip makers and QTLs for grain length, co-detected by all GAPIT models on chromosomes (Chr) 1-3, 5, 7, and 11, were qGL1-1BFSG (AX-95918134, Chr1: 3,820,526 bp) explains 65.2-72.5% of the phenotypic variance explained (PVE). In addition, qGW1-1BFSG (AX-273945773, Chr1: 5,623,288 bp) for grain width explains 15.5-18.9% of PVE. Furthermore, BLINK or FarmCPU identified three QTLs for grain thickness independently, and explain 74.9% (qGT1Blink, AX-279261704, Chr1: 18,023,142 bp) and 54.9% (qGT2-1Farm, AX-154787777, Chr2: 2,118,477 bp) of the observed PVE. For the grain length-to-width ratio (LWR), the qLWR2BFSG (AX-274833045, Chr2: 10,000,097 bp) explains nearly 15.2-32% of the observed PVE. Likewise, the major QTL for thousand-grain weight (TGW) was detected on Chr6 (qTGW6BFSG, AX-115737727, 28,484,619 bp) and explains 32.8-54% of PVE. The qTGW6BFSG QTL coincides with qGW6-1Blink for grain width and explained 32.8-54% of PVE. Putative candidate genes pooled from major QTLs for each grain trait have interesting annotated functions that require functional studies to elucidate their function in the control of grain size, shape, or weight in rice. Genome selection analysis proposed makers useful for downstream marker-assisted selection based on genetic merit of RILs.
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BACKGROUND: Crop breeding should be accelerated to address global warming and climate change. Wheat (Triticum aestivum L.) is a major food crop. Speed breeding (SB) and speed vernalization (SV) techniques for spring and winter wheat have recently been established. However, there are few practical examples of these strategies being used economically and efficiently in breeding programs. We aimed to establish and evaluate the performance of a breeder-friendly and energy-saving generation acceleration system by modifying the SV + SB system. RESULTS: In this study, a four-generation advancement system for wheat (regardless of its growth habits) was established and evaluated using an energy-efficient extended photoperiod treatment. A glasshouse with a 22-hour photoperiod that used 10 h of natural sunlight and 12 h of LED lights, and minimized temperature control during the winter season, was successful in accelerating generation. Even with one or two field tests, modified speed breeding (mSB) combined with a speed vernalization system (SV + mSB) reduced breeding time by more than half compared to traditional field-based methods. When compared to the existing SV + SB system, the SV + mSB system reduced energy use by 80% to maintain a 22-hour photoperiod. Significant correlations were found between the SV + mSB and field conditions in the number of days to heading (DTH) and culm length (CL). Genetic resources, recombinant inbred lines, and breeding materials that exhibited shorter DTH and CL values under SV + mSB conditions showed the same pattern in the field. CONCLUSIONS: The results of our SV + mSB model, as well as its practical application in wheat breeding programs, are expected to help breeders worldwide incorporate generation acceleration systems into their conventional breeding programs.
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The tumor-suppressor breast cancer 1 (BRCA1) in complex with BRCA1-associated really interesting new gene (RING) domain 1 (BARD1) is a RING-type ubiquitin E3 ligase that modifies nucleosomal histone and other substrates. The importance of BRCA1-BARD1 E3 activity in tumor suppression remains highly controversial, mainly stemming from studying mutant ligase-deficient BRCA1-BARD1 species that we show here still retain significant ligase activity. Using full-length BRCA1-BARD1, we establish robust BRCA1-BARD1-mediated ubiquitylation with specificity, uncover multiple modes of activity modulation, and construct a truly ligase-null variant and a variant specifically impaired in targeting nucleosomal histones. Cells expressing either of these BRCA1-BARD1 separation-of-function alleles are hypersensitive to DNA-damaging agents. Furthermore, we demonstrate that BRCA1-BARD1 ligase is not only required for DNA resection during homology-directed repair (HDR) but also contributes to later stages for HDR completion. Altogether, our findings reveal crucial, previously unrecognized roles of BRCA1-BARD1 ligase activity in genome repair via HDR, settle prior controversies regarding BRCA1-BARD1 ligase functions, and catalyze new efforts to uncover substrates related to tumor suppression.
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Neoplasias , Proteínas Supresoras de Tumor , Humanos , Proteínas Supresoras de Tumor/metabolismo , Proteína BRCA1/metabolismo , Ubiquitinación , Histonas/genética , Histonas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Reparación del ADN por Recombinación , ADN , Reparación del ADNRESUMEN
Environmental agents like ionizing radiation (IR) and chemotherapeutic drugs can cause severe damage to the DNA, often in the form of double-strand breaks (DSBs). Remaining unrepaired, DSBs can lead to chromosomal rearrangements, and cell death. One major error-free pathway to repair DSBs is homologous recombination repair (HRR). Tousled-like kinase 1 (TLK1), a Ser/Thr kinase that regulates the DNA damage checkpoint, has been found to interact with RAD54, a central DNA translocase in HRR. To determine how TLK1 regulates RAD54, we inhibited or depleted TLK1 and tested how this impacts HRR in human cells using a ISce-I-GR-DsRed fused reporter endonuclease. Our results show that TLK1 phosphorylates RAD54 at three threonines (T41, T59 and T700), two of which are located within its N-terminal domain (NTD) and one is located within its C-terminal domain (CTD). Phosphorylation at both T41 and T59 supports HRR and protects cells from DNA DSB damage. In contrast, phosphorylation of T700 leads to impaired HRR and engenders no protection to cells from cytotoxicity and rather results in repair delay. Further, our work enlightens the effect of RAD54-T700 (RAD54-CTD) phosphorylation by TLK1 in mammalian system and reveals a new site of interaction with RAD51.
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Reparación del ADN , Reparación del ADN por Recombinación , Animales , Humanos , Fosforilación , Daño del ADN , ADN/metabolismo , Recombinasa Rad51/metabolismo , Recombinación Homóloga , Mamíferos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
Break-induced telomere synthesis (BITS) is a RAD51-independent form of break-induced replication that contributes to alternative lengthening of telomeres1,2. This homology-directed repair mechanism utilizes a minimal replisome comprising proliferating cell nuclear antigen (PCNA) and DNA polymerase-δ to execute conservative DNA repair synthesis over many kilobases. How this long-tract homologous recombination repair synthesis responds to complex secondary DNA structures that elicit replication stress remains unclear3-5. Moreover, whether the break-induced replisome orchestrates additional DNA repair events to ensure processivity is also unclear. Here we combine synchronous double-strand break induction with proteomics of isolated chromatin segments (PICh) to capture the telomeric DNA damage response proteome during BITS1,6. This approach revealed a replication stress-dominated response, highlighted by repair synthesis-driven DNA damage tolerance signalling through RAD18-dependent PCNA ubiquitination. Furthermore, the SNM1A nuclease was identified as the major effector of ubiquitinated PCNA-dependent DNA damage tolerance. SNM1A recognizes the ubiquitin-modified break-induced replisome at damaged telomeres, and this directs its nuclease activity to promote resection. These findings show that break-induced replication orchestrates resection-dependent lesion bypass, with SNM1A nuclease activity serving as a critical effector of ubiquitinated PCNA-directed recombination in mammalian cells.
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Roturas del ADN de Doble Cadena , Reparación del ADN , Replicación del ADN , Recombinación Homóloga , Telómero , Moldes Genéticos , Animales , Proteínas de Ciclo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , ADN Polimerasa III/metabolismo , Proteínas de Unión al ADN/metabolismo , Exodesoxirribonucleasas/metabolismo , Mamíferos , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteómica , Recombinasa Rad51/metabolismo , Telómero/genética , Telómero/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Homologous recombination (HR) fulfils a pivotal role in the repair of DNA double-strand breaks and collapsed replication forks1. HR depends on the products of several paralogues of RAD51, including the tetrameric complex of RAD51B, RAD51C, RAD51D and XRCC2 (BCDX2)2. BCDX2 functions as a mediator of nucleoprotein filament assembly by RAD51 and single-stranded DNA (ssDNA) during HR, but its mechanism remains undefined. Here we report cryogenic electron microscopy reconstructions of human BCDX2 in apo and ssDNA-bound states. The structures reveal how the amino-terminal domains of RAD51B, RAD51C and RAD51D participate in inter-subunit interactions that underpin complex formation and ssDNA-binding specificity. Single-molecule DNA curtain analysis yields insights into how BCDX2 enhances RAD51-ssDNA nucleoprotein filament assembly. Moreover, our cryogenic electron microscopy and functional analyses explain how RAD51C alterations found in patients with cancer3-6 inactivate DNA binding and the HR mediator activity of BCDX2. Our findings shed light on the role of BCDX2 in HR and provide a foundation for understanding how pathogenic alterations in BCDX2 impact genome repair.
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Proteínas de Unión al ADN , Recombinación Homóloga , Complejos Multiproteicos , Humanos , Microscopía por Crioelectrón , Replicación del ADN , ADN de Cadena Simple/química , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , ADN de Cadena Simple/ultraestructura , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/ultraestructura , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Complejos Multiproteicos/ultraestructura , Neoplasias/genética , Nucleoproteínas/metabolismo , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , Recombinasa Rad51/química , Recombinasa Rad51/metabolismo , Recombinasa Rad51/ultraestructura , Especificidad por SustratoRESUMEN
Pif1 is a broadly conserved helicase that is essential for genome integrity and participates in numerous aspects of DNA metabolism, including telomere length regulation, Okazaki fragment maturation, replication fork progression through difficult-to-replicate sites, replication fork convergence, and break-induced replication. However, details of its translocation properties and the importance of amino acids residues implicated in DNA binding remain unclear. Here, we use total internal reflection fluorescence microscopy with single-molecule DNA curtain assays to directly observe the movement of fluorescently tagged Saccharomyces cerevisiae Pif1 on single-stranded DNA (ssDNA) substrates. We find that Pif1 binds tightly to ssDNA and translocates very rapidly (â¼350 nucleotides per second) in the 5'â3' direction over relatively long distances (â¼29,500 nucleotides). Surprisingly, we show the ssDNA-binding protein replication protein A inhibits Pif1 activity in both bulk biochemical and single-molecule measurements. However, we demonstrate Pif1 can strip replication protein A from ssDNA, allowing subsequent molecules of Pif1 to translocate unimpeded. We also assess the functional attributes of several Pif1 mutations predicted to impair contact with the ssDNA substrate. Taken together, our findings highlight the functional importance of these amino acid residues in coordinating the movement of Pif1 along ssDNA.
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ADN de Cadena Simple , Proteínas de Saccharomyces cerevisiae , ADN/metabolismo , Replicación del ADN , ADN de Cadena Simple/genética , ADN de Cadena Simple/metabolismo , Nucleótidos/metabolismo , Proteína de Replicación A/genética , Proteína de Replicación A/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMEN
The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.
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Replicación del ADN , Recombinasa Rad51 , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismo , Reparación del ADN , Proteína BRCA2/metabolismo , ADN , Recombinación HomólogaRESUMEN
Nitric oxide (NO), an ancient molecule with multiple roles in plants, has gained momentum and continues to govern plant biosciences-related research. NO, known to be involved in diverse physiological and biological processes, is a central molecule mediating cellular redox homeostasis under abiotic and biotic stresses. NO signaling interacts with various signaling networks to govern the adaptive response mechanism towards stress tolerance. Although diverging views question the role of plants in the current greenhouse gases (GHGs) budget, it is widely accepted that plants contribute, in one way or another, to the release of GHGs (carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O) and ozone (O3)) to the atmosphere, with CH4 and N2O being the most abundant, and occur simultaneously. Studies support that elevated concentrations of GHGs trigger similar signaling pathways to that observed in commonly studied abiotic stresses. In the process, NO plays a forefront role, in which the nitrogen metabolism is tightly related. Regardless of their beneficial roles in plants at a certain level of accumulation, high concentrations of CO2, CH4, and N2O-mediating stress in plants exacerbate the production of reactive oxygen (ROS) and nitrogen (RNS) species. This review assesses and discusses the current knowledge of NO signaling and its interaction with other signaling pathways, here focusing on the reported calcium (Ca2+) and hormonal signaling, under elevated GHGs along with the associated mechanisms underlying GHGs-induced stress in plants.
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DNA lesions induced by alkylating agents are repaired by two canonical mechanisms, base excision repair dependent on poly(ADP) ribose polymerase 1 (PARP1) and the other mediated by O6-methylguanine (O6meG)-DNA methyltransferase (MGMT) in a single-step catalysis of alkyl-group removal. O6meG is the most cytotoxic and mutagenic lesion among the methyl adducts induced by alkylating agents. Although it can accomplish the dealkylation reaction all by itself as a single protein without associating with other repair proteins, evidence is accumulating that MGMT can form complexes with repair proteins and is highly regulated by a variety of post-translational modifications, such as phosphorylation, ubiquitination, and others. Here, we show that PARP1 and MGMT proteins interact directly in a non-catalytic manner, that MGMT is subject to PARylation by PARP1 after DNA damage, and that the O6meG repair is enhanced upon MGMT PARylation. We provide the first evidence for the direct DNA-independent PARP1-MGMT interaction. Further, PARP1 and MGMT proteins also interact via PARylation of MGMT leading to formation of a novel DNA damage inducible PARP1-MGMT protein complex. This catalytic interaction activates O6meG repair underpinning the functional crosstalk between base excision and MGMT-mediated DNA repair mechanisms. Furthermore, clinically relevant 'chronic' temozolomide exposure induced PARylation of MGMT and increased binding of PARP1 and MGMT to chromatin in cells. Thus, we provide the first mechanistic description of physical interaction between PARP1 and MGMT and their functional cooperation through PARylation for activation of O6meG repair. Hence, the PARP1-MGMT protein complex could be targeted for the development of advanced and more effective cancer therapeutics, particularly for cancers sensitive to PARP1 and MGMT inhibition.