The serine/threonine kinase CHK2 is a keycomponent of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates 〉20 proteins to induce the appropriate cellular response...The serine/threonine kinase CHK2 is a keycomponent of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates 〉20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In par- ticular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy.展开更多
Hand,foot,and mouth disease(HFMD)is a contagious disease mainly occurring in young children,and outbreaks commonly occur among young children in the Asia–Pacific region including Thailand.Moreover,the World Health Or...Hand,foot,and mouth disease(HFMD)is a contagious disease mainly occurring in young children,and outbreaks commonly occur among young children in the Asia–Pacific region including Thailand.Moreover,the World Health Organization(WHO)monitors HFMD in the Western Pacific region to detect outbreaks and other significant events by the Regional Event Based Surveillance System.HFMD is mainly caused by a group of enteroviruses(EVs)transmitted through direct contact(person to person)and indirect contact with contaminated objects(surface-to-hand).However,few studies have examined the surface stability of EVs.In this study,we investigated the stability of enterovirus A71(EV-A71)and coxsackievirus A16(CVA16)on three different dry surfaces(wood,plastic,and stainless steel)using the endpoint titration using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)staining of viable cells and real-time polymerase chain reaction(viral genome detection).The results revealed that virus infectivity dramatically decreased within a few hours on dry surfaces.However,viral RNA could be detected on dry surfaces for up to 28 days.Concerning heat inactivation,both EV-A71 and CVA16 were inactivated after exposure to 60°C for 15 min.Information on virus stability on different dry surfaces will provide useful information for HFMD transmission control.展开更多
While Mek1/2 and Gsk3βinhibition("2i")supports the maintenance of murine embryonic stem cells(EsCs)in a homogenous naive state,prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impa...While Mek1/2 and Gsk3βinhibition("2i")supports the maintenance of murine embryonic stem cells(EsCs)in a homogenous naive state,prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential.Additionally,2i fails to support derivation and culture of fully potent female ESCs.Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin(AlbuMAx)undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture.Mechanisticaily,lipids in AlbuMAx impact intracellular metabolism including nucleotide biosynthesis,lipid biogenesis,and TCA cycle intermediates,with enhanced expression of DNMT3s that prevent DNA hypomethylation.Lipids induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation,which also alleviates X chromosome loss in female ESCs.Importantly,both male and female"all-ESc"mice can be generated from de novo derived ESCs using AlbuMAXbased media.Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.展开更多
The phytohormone abscisic acid （ABA） regulates many aspects of division. Previous study indicates that ABA treatment increases DNA plant growth, including seed germination, root growth and cell damage and somatic ho...The phytohormone abscisic acid （ABA） regulates many aspects of division. Previous study indicates that ABA treatment increases DNA plant growth, including seed germination, root growth and cell damage and somatic homologous recombination （HR） in Arabi- dopsis abo4/pol ε （aba overly-sensitive 4/DNA polymerase ε） mutants. DNA replication factor C （RFC） complex is required for loading PCNA （Proliferating Cell Nuclear Antigen） during DNA replication. The defect in RFC1, the largest subunit of RFC, causes the high HR and DNA damage sensitivity in Arabidopsis. Here we found that like pol e/abo4, rfcl is sensitive to ABA in both ABA-inhibiting seed germination and root growth. However, ABA treatment greatly reduces HR and also reduces the expression of the DNA-damaged marker genes in ,rfcl. These results suggest that RFCI plays critical roles in ABA-mediated HR in Arabidopsis.展开更多
Barley(Hordeum vulgare L.)is one of the most Aluminum(Al)sensitive cereal species.In this study,the physiological,biochemical,and molecular response of barley seedlings to Al treatment was examined to gain insight int...Barley(Hordeum vulgare L.)is one of the most Aluminum(Al)sensitive cereal species.In this study,the physiological,biochemical,and molecular response of barley seedlings to Al treatment was examined to gain insight into Al response and tolerance mechanisms.The results showed that superoxide dismutase(SOD),peroxidase(POD)and catalase(CAT)activity were inhibited to different degrees following Al exposure.The MDA content also significantly increased with increasing Al concentrations.SRAP results indicated significant differences between Al treatments and controls in terms of SRAP profile,and the genomic template stability(GTS)decreased with increasing Al concentration and duration.These integrative results help to elucidate the underlying mechanisms that the barley response to Al toxicity.展开更多
文摘The serine/threonine kinase CHK2 is a keycomponent of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates 〉20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In par- ticular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy.
文摘Hand,foot,and mouth disease(HFMD)is a contagious disease mainly occurring in young children,and outbreaks commonly occur among young children in the Asia–Pacific region including Thailand.Moreover,the World Health Organization(WHO)monitors HFMD in the Western Pacific region to detect outbreaks and other significant events by the Regional Event Based Surveillance System.HFMD is mainly caused by a group of enteroviruses(EVs)transmitted through direct contact(person to person)and indirect contact with contaminated objects(surface-to-hand).However,few studies have examined the surface stability of EVs.In this study,we investigated the stability of enterovirus A71(EV-A71)and coxsackievirus A16(CVA16)on three different dry surfaces(wood,plastic,and stainless steel)using the endpoint titration using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)staining of viable cells and real-time polymerase chain reaction(viral genome detection).The results revealed that virus infectivity dramatically decreased within a few hours on dry surfaces.However,viral RNA could be detected on dry surfaces for up to 28 days.Concerning heat inactivation,both EV-A71 and CVA16 were inactivated after exposure to 60°C for 15 min.Information on virus stability on different dry surfaces will provide useful information for HFMD transmission control.
基金supported by the New York State Stem Cell Science Program under contract C32581GGthe National Institutes of Health under award numbers:1 R01 GM129380-01 and 1R210OD031973-01 (to D.W.).
文摘While Mek1/2 and Gsk3βinhibition("2i")supports the maintenance of murine embryonic stem cells(EsCs)in a homogenous naive state,prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental potential.Additionally,2i fails to support derivation and culture of fully potent female ESCs.Here we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin(AlbuMAx)undergo pluripotency transition yet maintain genomic stability and full potency over long-term culture.Mechanisticaily,lipids in AlbuMAx impact intracellular metabolism including nucleotide biosynthesis,lipid biogenesis,and TCA cycle intermediates,with enhanced expression of DNMT3s that prevent DNA hypomethylation.Lipids induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation,which also alleviates X chromosome loss in female ESCs.Importantly,both male and female"all-ESc"mice can be generated from de novo derived ESCs using AlbuMAXbased media.Our findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.
文摘The phytohormone abscisic acid （ABA） regulates many aspects of division. Previous study indicates that ABA treatment increases DNA plant growth, including seed germination, root growth and cell damage and somatic homologous recombination （HR） in Arabi- dopsis abo4/pol ε （aba overly-sensitive 4/DNA polymerase ε） mutants. DNA replication factor C （RFC） complex is required for loading PCNA （Proliferating Cell Nuclear Antigen） during DNA replication. The defect in RFC1, the largest subunit of RFC, causes the high HR and DNA damage sensitivity in Arabidopsis. Here we found that like pol e/abo4, rfcl is sensitive to ABA in both ABA-inhibiting seed germination and root growth. However, ABA treatment greatly reduces HR and also reduces the expression of the DNA-damaged marker genes in ,rfcl. These results suggest that RFCI plays critical roles in ABA-mediated HR in Arabidopsis.
基金This research was funded by National Key Technology Research and Development Program(2015BAD01B02)the National Natural Science Foundation of China(31401316).
文摘Barley(Hordeum vulgare L.)is one of the most Aluminum(Al)sensitive cereal species.In this study,the physiological,biochemical,and molecular response of barley seedlings to Al treatment was examined to gain insight into Al response and tolerance mechanisms.The results showed that superoxide dismutase(SOD),peroxidase(POD)and catalase(CAT)activity were inhibited to different degrees following Al exposure.The MDA content also significantly increased with increasing Al concentrations.SRAP results indicated significant differences between Al treatments and controls in terms of SRAP profile,and the genomic template stability(GTS)decreased with increasing Al concentration and duration.These integrative results help to elucidate the underlying mechanisms that the barley response to Al toxicity.
