The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. F...The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.展开更多
The double-stranded DNA (dsDNA) probe contains two different protein binding sites. One is for DNA- binding proteins to be detected and the other is for a DNA restriction enzyme. The two sites were arranged together w...The double-stranded DNA (dsDNA) probe contains two different protein binding sites. One is for DNA- binding proteins to be detected and the other is for a DNA restriction enzyme. The two sites were arranged together with no base interval. The working principle of the capturing dsDNA probe is described as follows: the capturing probe can be cut with the DNA restriction enzyme (such as EcoR I) to cause a sticky terminal, if the probe is not bound with a target protein, and the sticky terminal can be extended and labeled with Cy3-dUTP by DNA polymerase. When the probe is bound with a target protein, the probe is not capable to be cut by the restriction enzyme because of space obstruction. The amount of the target DNA binding proteins can be measured according to the variations of fluorescent signals of the corresponding probes.展开更多
Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Met...Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Methods： The data were collected and analyzed by retrieval of 229 published short dsRNAs designed for degradation ofHCV RNA. Results： Statistical analyses showed that the most frequently involved short dsRNAs were directing against 5＇NTR/core and genotype lb, accounting for 64.2% and 69.9%, respectively. Inhibitory efficacy varied with the structural characteristics of short dsRNAs, of which the most potential were those directed against HCV core region with inhibitory efficacy of 70.2%. Moreover, the mean inhibitory efficacy of short dsRNAs with GC contents from 30% to 52% was higher than that of those with GC contents out of this range. Conclusion： Based on this pooled data in a relatively large sample, the present results provided clues to design for short dsRNAs with more potent inhibitory efficacy.展开更多
Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein k...Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.展开更多
DNA damage response （DDR） in different cell cycle status of human peripheral blood lymphocytes （PBLs） and the role of H2AX in DDR were investigated. The PBLs were stimulated into cell cycle with phytohemagglutinin...DNA damage response （DDR） in different cell cycle status of human peripheral blood lymphocytes （PBLs） and the role of H2AX in DDR were investigated. The PBLs were stimulated into cell cycle with phytohemagglutinin （PHA）. The apoptotic ratio and the phosphorylation H2AX （S139） were flow cytometrically measured in resting and proliferating PBLs after treatment with camptothecin （CPT） or X-ray. The expressions of γH2AX, Bcl-2, caspase-3 and caspase-9 were detected by Western blotting. DDR in 293T cells was detected after H2AX was silenced by RNAi method. Our results showed that DNA double strand breaks （DSBs） were both induced in quiescent and proliferating PBLs after CPT or X-ray treatment. The phosphorylation of H2AX and apoptosis were more sensitive in proliferating PBLs compared with quiescent lymphocytes （P0.05）. The expression levels of anti-apoptotic proteins Bcl-2 were reduced and cleaved caspase-3 and caspase-9 were increased. No significant changes were observed in CPT-induced apoptosis in 293T cells between H2AX knocking down group and controls. It was concluded that proliferating PBLs were more vulnerable to DNA damage compared to non-stimulated lymphocytes and had higher apoptosis rates. γH2AX may only serve as a marker of DNA damage but exert no effect on apoptosis regulation.展开更多
RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Ch...RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Chrysomelidae family;however,whether this technology is suitable for controlling pests in the Coccinellidae remained unknown.The coccinellid 28-spotted potato ladybird(Henosepilachna vigintioctopunctata;HV)is a serious pest of solanaceous crops.In this study,we identified three efficient target genes(β-Actin,SRP54,and SNAP)for RNAi using in vitro double-stranded RNAs(dsRNAs)fed to HV,and found that dsRNAs targetingβ-Actin messenger RNA(dsACT)induced more potent RNAi than those targeting the other two genes.We next generated transplastomic and nuclear transgenic potato(Solanum tuberosum)plants expressing HV dsACT.Long dsACT stably accumulated to up to 0.7%of the total cellular RNA in the transplastomic plants,at least three orders of magnitude higher than in the nuclear transgenic plants.Notably,the transplastomic plants also exhibited a significantly stronger resistance to HV,killing all larvae within 6 d.Our data demonstrate the potential of PM-RNAi as an efficient pest control measure for HV,extending the application range of this technology to Coccinellidae pests.展开更多
Dear Editor,Varicella,also known as chickenpox,is caused by the varicella-zoster virus(VZV),which has a genome comprising 125 kb of linear double-stranded DNA encoding approximately 71 proteins,is highly contagious,an...Dear Editor,Varicella,also known as chickenpox,is caused by the varicella-zoster virus(VZV),which has a genome comprising 125 kb of linear double-stranded DNA encoding approximately 71 proteins,is highly contagious,and spreads from person to person through direct contact with the rash or through contact with aerosolized droplets.Unsurprisingly,groups of people,social interaction,and urbanization have been positively correlated with an increased incidence of varicella.Viral transmission also coincides with indoor activity and is increased among school children.展开更多
R-loops,three-strand nucleic acid structures,have emerged as crucial players in various physiological processes,including the regulation of gene expression,DNA replication,and class switch recombination.However,their ...R-loops,three-strand nucleic acid structures,have emerged as crucial players in various physiological processes,including the regulation of gene expression,DNA replication,and class switch recombination.However,their presence also poses a significant threat to genome stability.A particularly challenging aspect is understanding the dynamic balance between R-loops’“light”and“dark”sites,especially concerning maintaining genome integrity.The complex and multifaceted roles of R-loops in genome stability necessitate a deeper understanding.This review offers a comprehensive exploration of the formation,resolution,and implications of R-loops,particularly in the context of DNA damage and human disease.We delve into the dualistic nature of R-loops,highlighting their role in DNA damage response and repair,and discuss the therapeutic potential arising from our evolving understanding of these enigmatic entities.Emphasizing recent advancements and unresolved questions,this review aims to provide a cohesive overview of R-loops,inviting further inquiry and investigation into their complex biological significance.展开更多
DNA double-strand breaks(DSBs)severely impact the integrity of the genome and cell homeostasis.To address DSBs,cells activate sophisticated mechanisms to repair this DNA damage.Non-homologous end joining(NHEJ)is a pre...DNA double-strand breaks(DSBs)severely impact the integrity of the genome and cell homeostasis.To address DSBs,cells activate sophisticated mechanisms to repair this DNA damage.Non-homologous end joining(NHEJ)is a predominant pathway for repairing DSBs.p53 binding protein 1(53BP1)serves as a pivotal regulator in the NHEJ pathway.By locating and forming phase separation at DSB sites,53BP1 acts as a scaffold protein to recruit downstream components and facilitate DSB repair[1].展开更多
One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing(SIGS).In SIGS,small interfering RNA(siRNA)or double-stranded RNA(dsRNA)targeting essential or virulence-related ...One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing(SIGS).In SIGS,small interfering RNA(siRNA)or double-stranded RNA(dsRNA)targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference(RNAi)of the targeted genes,inhibiting fungal growth and disease.However,SIGS is limited by the unstable nature of RNA under environmental conditions.The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA,a formulation termed BioClay^(TM),can enhance RNA durability on plants,prolonging its activity against pathogens.Here,we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea,a major plant fungal pathogen,on tomato leaves and fruit and on mature chickpea plants.BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits,when compared with naked dsRNA.In flowering chickpea plants,BioClay provided prolonged protection for up to 4 weeks,covering the critical period of poding,whereas naked dsRNA provided limited protection.This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.展开更多
RecQ5 in mammalian cells has been suggested to suppress inappropriate homologous recombination.However,the specific pathway(s)in which it is involved and the underlining mechanism(s)remain poorly understood.We took ad...RecQ5 in mammalian cells has been suggested to suppress inappropriate homologous recombination.However,the specific pathway(s)in which it is involved and the underlining mechanism(s)remain poorly understood.We took advantage of genetic tools in Drosophila to investigate how Drosophila RecQ5(dRecQ5)functions in vivo in homologous recombination-mediated double strand break(DSB)repair.We generated null alleles of dRecQ5 using the targeted recombination technique.The mutant animals are homozygous viable,but with growth retardation during development.The mutants are sensitive to both exogenous DSB-inducing treatment,such as gamma-irradiation,and endogenously induced double strand breaks(DSBs)by I-Sce I endonuclease.In the absence of dRecQ5,single strand annealing(SSA)-mediated DSB repair is compromised with compensatory increases in either inter-homologous gene conversion,or non-homologous end joining(NHEJ)when inter-chromosomal homologous sequence is unavailable.Loss of function of dRecQ5 also leads to genome instability in loss of heterozygosity(LOH)assays.Together,our data demonstrate that dRecQ5 functions in SSA-mediated DSB repair to achieve its full efficiency and in suppression of LOH in Drosophila.展开更多
Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago.Chromosomal translocations,a type of particular structural changes involving heterologous chromo...Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago.Chromosomal translocations,a type of particular structural changes involving heterologous chromosomes,have made a critical impact on diagnosis,prognosis and treatment of cancers.For example,the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia.In the past few decades,tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations.This review focuses on the basic mechanisms underlying the generation of chromosomal translocations.In particular,the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.展开更多
The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attrib...The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage.Here,we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance.We discuss the implications,with a particular focus on epigenetic modifications and H3K4 methylation.We also deliberate on the mechanisms responsible,the consequences for the refinement of PARP inhibitor use in the clinic,and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.展开更多
文摘The genomes of eukaryotic cells are under continuous assault by environmental agents and endogenous metabolic byproducts. Damage induced in DNA usually leads to a cascade of cellular events, the DNA damage response. Failure of the DNA damage response can lead to development of malignancy by reducing the efficiency and fidelity of DNA repair. The NBS1 protein is a component of the MRE11/RAD50/NBS 1 complex （MRN） that plays a critical role in the cellular response to DNA damage and the maintenance of chromosomal integrity. Mutations in the NBS1 gene are responsible for Nijmegen breakage syndrome （NBS）, a hereditary disorder that imparts an increased predisposition to development of malignancy. The phenotypic characteristics of cells isolated from NBS patients point to a deficiency in the repair of DNA double strand breaks. Here, we review the current knowledge of the role of NBS1 in the DNA damage response. Emphasis is placed on the role of NBS1 in the DNA double strand repair, modulation of the DNA damage sensing and signaling, cell cycle checkpoint control and maintenance oftelomere stability.
文摘The double-stranded DNA (dsDNA) probe contains two different protein binding sites. One is for DNA- binding proteins to be detected and the other is for a DNA restriction enzyme. The two sites were arranged together with no base interval. The working principle of the capturing dsDNA probe is described as follows: the capturing probe can be cut with the DNA restriction enzyme (such as EcoR I) to cause a sticky terminal, if the probe is not bound with a target protein, and the sticky terminal can be extended and labeled with Cy3-dUTP by DNA polymerase. When the probe is bound with a target protein, the probe is not capable to be cut by the restriction enzyme because of space obstruction. The amount of the target DNA binding proteins can be measured according to the variations of fluorescent signals of the corresponding probes.
基金Supported by Grants from the Committee of Science and Technology of Shanghai, China (No.10ZR1413100, and No.114119a1400)
文摘Objective： To describe the characteristics of short interfering double stranded RNA （dsRNA） against hepatitis C virus （HCV） and to fred out the determining factors in design for desirable inhibitory efficacy. Methods： The data were collected and analyzed by retrieval of 229 published short dsRNAs designed for degradation ofHCV RNA. Results： Statistical analyses showed that the most frequently involved short dsRNAs were directing against 5＇NTR/core and genotype lb, accounting for 64.2% and 69.9%, respectively. Inhibitory efficacy varied with the structural characteristics of short dsRNAs, of which the most potential were those directed against HCV core region with inhibitory efficacy of 70.2%. Moreover, the mean inhibitory efficacy of short dsRNAs with GC contents from 30% to 52% was higher than that of those with GC contents out of this range. Conclusion： Based on this pooled data in a relatively large sample, the present results provided clues to design for short dsRNAs with more potent inhibitory efficacy.
文摘Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.
基金supported by grants from Program 973 from Ministry of ScienceTechnology of China (Nos. 2004CB518705, 2009CB5218702)the National Natural Sciences Foundation of China (Nos. 30872472, 30800569)
文摘DNA damage response （DDR） in different cell cycle status of human peripheral blood lymphocytes （PBLs） and the role of H2AX in DDR were investigated. The PBLs were stimulated into cell cycle with phytohemagglutinin （PHA）. The apoptotic ratio and the phosphorylation H2AX （S139） were flow cytometrically measured in resting and proliferating PBLs after treatment with camptothecin （CPT） or X-ray. The expressions of γH2AX, Bcl-2, caspase-3 and caspase-9 were detected by Western blotting. DDR in 293T cells was detected after H2AX was silenced by RNAi method. Our results showed that DNA double strand breaks （DSBs） were both induced in quiescent and proliferating PBLs after CPT or X-ray treatment. The phosphorylation of H2AX and apoptosis were more sensitive in proliferating PBLs compared with quiescent lymphocytes （P0.05）. The expression levels of anti-apoptotic proteins Bcl-2 were reduced and cleaved caspase-3 and caspase-9 were increased. No significant changes were observed in CPT-induced apoptosis in 293T cells between H2AX knocking down group and controls. It was concluded that proliferating PBLs were more vulnerable to DNA damage compared to non-stimulated lymphocytes and had higher apoptosis rates. γH2AX may only serve as a marker of DNA damage but exert no effect on apoptosis regulation.
基金supported by grants from the Natural Science Foundation of Hubei Province(2020CFA012)the National Natural Science Foundation of China(32271912)to J.Z。
文摘RNA interference(RNAi)has emerged as a powerful technology for pest management.Previously,we have shown that plastid-mediated RNAi(PM-RNAi)can be utilized to control the Colorado potato beetle,an insect pest in the Chrysomelidae family;however,whether this technology is suitable for controlling pests in the Coccinellidae remained unknown.The coccinellid 28-spotted potato ladybird(Henosepilachna vigintioctopunctata;HV)is a serious pest of solanaceous crops.In this study,we identified three efficient target genes(β-Actin,SRP54,and SNAP)for RNAi using in vitro double-stranded RNAs(dsRNAs)fed to HV,and found that dsRNAs targetingβ-Actin messenger RNA(dsACT)induced more potent RNAi than those targeting the other two genes.We next generated transplastomic and nuclear transgenic potato(Solanum tuberosum)plants expressing HV dsACT.Long dsACT stably accumulated to up to 0.7%of the total cellular RNA in the transplastomic plants,at least three orders of magnitude higher than in the nuclear transgenic plants.Notably,the transplastomic plants also exhibited a significantly stronger resistance to HV,killing all larvae within 6 d.Our data demonstrate the potential of PM-RNAi as an efficient pest control measure for HV,extending the application range of this technology to Coccinellidae pests.
文摘Dear Editor,Varicella,also known as chickenpox,is caused by the varicella-zoster virus(VZV),which has a genome comprising 125 kb of linear double-stranded DNA encoding approximately 71 proteins,is highly contagious,and spreads from person to person through direct contact with the rash or through contact with aerosolized droplets.Unsurprisingly,groups of people,social interaction,and urbanization have been positively correlated with an increased incidence of varicella.Viral transmission also coincides with indoor activity and is increased among school children.
基金supported by research funding from the National Natural Science Foundation of China(No.32201061)the Natural Science Foundation of Shandong,China(No.ZR2021QC083).
文摘R-loops,three-strand nucleic acid structures,have emerged as crucial players in various physiological processes,including the regulation of gene expression,DNA replication,and class switch recombination.However,their presence also poses a significant threat to genome stability.A particularly challenging aspect is understanding the dynamic balance between R-loops’“light”and“dark”sites,especially concerning maintaining genome integrity.The complex and multifaceted roles of R-loops in genome stability necessitate a deeper understanding.This review offers a comprehensive exploration of the formation,resolution,and implications of R-loops,particularly in the context of DNA damage and human disease.We delve into the dualistic nature of R-loops,highlighting their role in DNA damage response and repair,and discuss the therapeutic potential arising from our evolving understanding of these enigmatic entities.Emphasizing recent advancements and unresolved questions,this review aims to provide a cohesive overview of R-loops,inviting further inquiry and investigation into their complex biological significance.
基金supported by the National Natural Science Foundation of China(32422041,32071226)the Foundation of Hubei Hongshan Laboratory(2021HSZD011)+1 种基金the Fundamental Research Funds for the Central Universities(2662023PY001)the HZAU-AGIS Cooperation Fund(SZYJY2022022).
文摘DNA double-strand breaks(DSBs)severely impact the integrity of the genome and cell homeostasis.To address DSBs,cells activate sophisticated mechanisms to repair this DNA damage.Non-homologous end joining(NHEJ)is a predominant pathway for repairing DSBs.p53 binding protein 1(53BP1)serves as a pivotal regulator in the NHEJ pathway.By locating and forming phase separation at DSB sites,53BP1 acts as a scaffold protein to recruit downstream components and facilitate DSB repair[1].
基金partially supported by the Australian Research Council Research Hub for Sustainable Crop Protection(IH190100022)funded by the Australian GovernmentNational Institute of Health(R35GM136379)+5 种基金National Science Foundation(IOS 2020731)United State Department of Agriculture(2021-67013-34258)the CIFAR‘Fungal Kingdom’fellowship to H.J.supported by MINECO(PID2019-110459RB-I00)MICINN(PLEC2021-008076)supported by an Advance Queensland Industry Research Fellowship。
文摘One of the most promising tools for the control of fungal plant diseases is spray-induced gene silencing(SIGS).In SIGS,small interfering RNA(siRNA)or double-stranded RNA(dsRNA)targeting essential or virulence-related pathogen genes are exogenously applied to plants and postharvest products to trigger RNA interference(RNAi)of the targeted genes,inhibiting fungal growth and disease.However,SIGS is limited by the unstable nature of RNA under environmental conditions.The use of layered double hydroxide or clay particles as carriers to deliver biologically active dsRNA,a formulation termed BioClay^(TM),can enhance RNA durability on plants,prolonging its activity against pathogens.Here,we demonstrate that dsRNA delivered as BioClay can prolong protection against Botrytis cinerea,a major plant fungal pathogen,on tomato leaves and fruit and on mature chickpea plants.BioClay increased the protection window from 1 to 3 weeks on tomato leaves and from 5 to 10 days on tomato fruits,when compared with naked dsRNA.In flowering chickpea plants,BioClay provided prolonged protection for up to 4 weeks,covering the critical period of poding,whereas naked dsRNA provided limited protection.This research represents a major step forward for the adoption of SIGS as an eco-friendly alternative to traditional fungicides.
基金This work has been financially supported by the National Basic Research Program(973 Program)(Nos.2009CB918702,2005CB522804)the National Natural Science Foundation of China(Grant Nos.30623005,90608029 and 30771217)Chinese Academy of Sciences(KSCX1-YW-R-70).
文摘RecQ5 in mammalian cells has been suggested to suppress inappropriate homologous recombination.However,the specific pathway(s)in which it is involved and the underlining mechanism(s)remain poorly understood.We took advantage of genetic tools in Drosophila to investigate how Drosophila RecQ5(dRecQ5)functions in vivo in homologous recombination-mediated double strand break(DSB)repair.We generated null alleles of dRecQ5 using the targeted recombination technique.The mutant animals are homozygous viable,but with growth retardation during development.The mutants are sensitive to both exogenous DSB-inducing treatment,such as gamma-irradiation,and endogenously induced double strand breaks(DSBs)by I-Sce I endonuclease.In the absence of dRecQ5,single strand annealing(SSA)-mediated DSB repair is compromised with compensatory increases in either inter-homologous gene conversion,or non-homologous end joining(NHEJ)when inter-chromosomal homologous sequence is unavailable.Loss of function of dRecQ5 also leads to genome instability in loss of heterozygosity(LOH)assays.Together,our data demonstrate that dRecQ5 functions in SSA-mediated DSB repair to achieve its full efficiency and in suppression of LOH in Drosophila.
基金supported by University of Colorado School of Medicine start-up fundLeukemia Research FoundationBoettcher Foundation for J.H.W.J.H.W.is a recipient of Boettcher Foundation Webb-Waring Biomedical Research Award.
文摘Chromosomal aberrations have been associated with cancer development since their discovery more than a hundred years ago.Chromosomal translocations,a type of particular structural changes involving heterologous chromosomes,have made a critical impact on diagnosis,prognosis and treatment of cancers.For example,the discovery of translocation between chromosomes 9 and 22 and the subsequent success of targeting the fusion product BCR-ABL transformed the therapy for chronic myelogenous leukemia.In the past few decades,tremendous progress has been achieved towards elucidating the mechanism causing chromosomal translocations.This review focuses on the basic mechanisms underlying the generation of chromosomal translocations.In particular,the contribution of frequency of DNA double strand breaks and spatial proximity of translocating loci is discussed.
基金supported by a PhD studentship from the University of Birmingham and Cancer Research UK(C17422/A25154)awarded to Sweatman E and Higgs MRa Breast Cancer Now project grant(2019AugPR1320)supporting Bayley R(awarded to Garcia P)an MRC Career Development Fellowship(MR/P009085/1)awarded to Higgs MR.
文摘The clinical treatment of DNA-repair defective tumours has been revolutionised by the use of poly(ADP)ribose polymerase(PARP)inhibitors.However,the efficacy of these compounds is hampered by resistance,which is attributed to numerous mechanisms including rewiring of the DNA damage response to favour pathways that repair PARP inhibitor-mediated damage.Here,we comment on recent findings by our group identifying the lysine methyltransferase SETD1A as a novel factor that conveys PARPi resistance.We discuss the implications,with a particular focus on epigenetic modifications and H3K4 methylation.We also deliberate on the mechanisms responsible,the consequences for the refinement of PARP inhibitor use in the clinic,and future possibilities to circumvent drug resistance in DNA-repair deficient cancers.
