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Inhibition of DNA polymerasepand of bleomycin repair synthesis in CHO cells ex<a href="https://www.ncbi.nlm.nih.gov/pubmed/24045179">sellRibociclib</a> hibited very similar sensitivities to inhibition by ddTTP. In H F cells, repair synthesis induced by bleomycin and neocar zinostatin were inhibited by and p ddTTP, respectively; however, repair synthesis induced by me thy la t ing agents and UV irradiation required much higher concen trations of ddTTP studies demonstrateth atDNA repair synthesis induced by bleomycin or neocarzinostaiin is much more sensitive to ddTTP inhibition than is repair synthesis induced by NMU, MNNG, or UV irradiation.The concentration of inhibitors which reduce the activity of purified hamster liver DNA polymerasep is also indicated.The ability of neocarzinostatin to damage DNA was dependent on reducing agents and was strongly inhibited by NEM; therefore, the sensitivity of neocarzinostatinin duced repair synthesis   to NEM was not reported.HI? cells were trea ted with different concentrations of MNNG and bleomycin and the amountof DNA damage was estimated.MNNG methylates thefollowing DNA bases; gua nine atN, adenine atN, and guanine at, in the relative proportions, respectively. Subsequent trea tmentof the DNA with alkali results in specifically cleaving the DNA atapurinic sites.TheDNA from control, MNNG, and bleomycintreated cells was isolated asdescribed, which involved heating at C, for h, and analyzed on alkaline sucrose gradients.Al though different concentrations of bleomycin and MNNG altered the amount of DNA damage, the ability of DNA polymerase inhibitors to decrease repair synthesis was not significantly affected by the amountof DNA damage. A primary role of DNA polymeraseyin repair synthesis would be indicated by inhibition of repair synthesis by relatively low concentrations of ddTTP aswell asNEM; however, such inhibition was not observed in repair synthesis induced by any of theagents studied. Repair synthesis induced by MNNG, NMU, or UV irradiation was relatively insensitive to ddTTP, whereas repair induced by bleomycin or neocar zinostatin was inhibited by much lower concentrations of ddTTP. Th is observation suggests thatdiffe rentDNA polymerases are involved in repairing different types of DNA damage.The similarity of ddTTP inhibition of neocarzin ostatin and bleomycin repair to the ddTTP inhibition of purified polymerase indicated th atpolymerase was primarily responsible for repair synthesis induced by these two agents.Although very high concentrations of araCTP inhibited repair synthesis induced by bleomycin and neocarzinostatin, similar conentrations of a raCTP also in hibited polymerase. It is difficult to explain why repair synthesis induced by neocarzinostatin and bleomycin was inhibited by high levels of aphidicolin, but purified polym erasepwas notinhibited by aphidicolin polymerase is required for one step in bleomycin or neocarzinostatin repair synthesis while polymerase a is required for a differentstep, polymerasep alone resynthesizes most of theDNA areas damaged by bleomycin and neocarzinostatin, and polymerase a alone re synthesizesother areas or in addition to polymerase a, aphidicolin in terac ts with ano ther cellular pro te in in such reduce polymerasepactivity in si tu. Indeed, a manner to decreased sensitivity of polymerase a to aphidicolin during purifkation hasbeen interpreted asloss of a polymerase a accessory protein which in terac ts with aphidicolin. Repair synthesis induced by MNNG, NMU, and UV irra diation were inhibited only by high concentrations of ddTTP, which also inhibits polymerase a.

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