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    2024-11-22

    39c60474-f3b3-4c57-9c34-9bff10caca2d

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    ???? ??? ??? ???? ???? ??? ???? ?? ????? ?????? ?? ????? ????? ??? ?????? ???? ???? ???? ??? ??? ???? ???? ?????? ?? ???? ??? ?????? ?????? ???? ?? ???? ?? ??? ????? ????? ??? ???

    ?????? ???? ??? ??? ?????, ???? ???, ?????????? ????? ?? ????? ??? ?? ????? ????? ??. ????? ?????? ???? ??? ?????? ?????? ??? ????? ?????? ?????? ?? ????? ?????? ??? ???? ??? ??? ????? ????? ??? ??? ????? ?????? ????? ??? ??? ????? ???? ? ???? ??? ?? ????? ???? ??? ??? ?? ?????? ??? ??? ???? ???? ????? ???? ?? ???? ??? ?????.

    ?.?.?. ????? 20? 2024 ? Wang Ping ??? ????? ?????? ????? ????? ??/10? ????? ??? ????? “Human HDAC6 senses valine abundancy to regulate DNA damage” ??? ??? ??? ????? ???? ?? ????? ???? ??????

    ?? ??? ?? ??? ???-????? ????? ????? Human deacetylase HDAC6? ?? ???? ??? ?? HDAC6 ???? ???? ???????? ?? ?? ????? ???? TET2 ??????? ????? ?? ????? ??? ???????

    ??????? ?? ????? ?? ?????? ?? ??? ?? ???? ????? ???? ???????? primate HDAC6 ????? ???-????? glutamate-tetranectide (SE14) ??? ???? ???? ?? ??? ?? ???? ???? ??????? ??? ???? ???? ????? ???? ??? ??? ? PARP ???? ???? ??? ????? ???? ??? ???? ??? ?????

    ?? ??? ?????? ???? ??????? ???? ?????? ????? ???? ???????? ??? ??? ????? ?? ???? ???? ???? ?????? ????? ? PARP ???? ?? ???? ??? ????? ??????

    1

    ???? ??? ???? ?????? ?? ??? ????? ????? ??? ??? ?? ??? ?? ???? ???? ??? ???? ????? ????? ?? ??? ????? ?????? ??????? ????? ??????

    ???-????? ?????? ???? ??? ???? ????? ??????? ??? ???????? ???? ???????? ?? ????? ???? ????? ????? ??? ?? ??? ???? ?? ???? ???? ?????? ?? ???? ????? ???? ?????

    ????? ?????? ???? ????? ? ?????? (VARS) ????? ??????? ?????6 ? VARS ?? ????? ???? ???? ??-??? ???? ??? ????? ???????? ????? ????? HDAC6 ???? ?Kd ≈ 2μM ?? ? isootope ???? ?????? ???????? ????? ?????? (????) ????? ?? ???? ?????? ????? ???? ??? ?????? ???????? ?????? ????? ???? ???? ???? ????? ????? ???? ???? ??????? ???? ??? ??????? ??? ?????? ??? ???? ????? ????? ???? ?????? ????? ????? ?????? ????? HDAC6 ???? ?????? ????? ?? ??? ?????? ??????? ?? ???? ????? ?????? ??????? ???????? ??????? ?HDAC6 knockout ???? ? mTOR ???? ????? ????? ???? ??? ???? ????? ??? ?? ???? ???? ????????? ???? ?????? ???? ??? ??? ???? ???? ???? ???? ??????

    ?HDAC6 ??? ???? ????? ?? ?? ???? ?????? ????? ????? HDAC6 ???? ? SE14 ?? ??? ?HDAC6 ?????? ????? ???? ??? ??? ???????? ?????? ?????? ???? ????? ????? ???? ? SE14 ?? ?HDAC6 ??? ?????? ??? ?? ?????? ??????? ??? ???? (?? ?? ??) HDAC6? ???? HDAC6 ???? ?? ??????? ?? ??? ???? ?????? ??? ????? ????? ???? ???? ???? ????, ??? ???? ???? ??? ???? ??? ??? ??? ?? ??????? ?????.

    HDAC6 ???? ???? ? SE14 ?? ??? ???????? ???? ?? ?????? ????? ? HDAC6 ?? ???? ???? ???? ???? ???? ??? ??? ???? ??? ??????? ?? ?????? ?? ????? ??? ?????? ?????? ?????? ????? ?? ??????6 ????????? ???? ??? ? SE14 ?? ??? ?? ?? ???-??? ?? ????? ????? ????-???? ??? ???? HDAC6 ?? ?????? ?????? ???????? ???????? ????? ???? ??? (DAC1 ?? DAC2) ????? ?????????????? TET2 ??? ??? (?? ??) ?? ??????? ? TET2 ? ????? ??????? ?? ????? ?????? ???????? ?????? ??? WGBS? ACE-Seq ?? MAB-Seq ?? ?????? ?????? ?????? ??????6-TET2 ???? ??? ??? ??? ????? ??????? ????? ??? ??? ????????? ???????? ??? ?? ????? ??????? ??? ???? ? ?? ? ??????? (TDG) ??? ?? ?? ?? ? ?????? ?????? ?????? ?? ????? ???-?? ??? ??????? ??????? TET2 ChIP-Seq? ? END-Seq ?? ddC S1 END-Seq ?? ????? ???? ???? ????? ????? ????????? ?????? ???? ???? ????? ?????? ????? ??? ???? ???? ??????????? (5fC/5caC) ???? ???????? ??? ??? ?? ?????? ???


    ??? ?? ???? ????? ?? ??? ??? ?????? ??? ??? ??? ????? ???? ?HDAC6-TET2-TDG ???? ????? ??? ??? ???????? ?????? ?? ?????? ?? ?????? ??? ?? ??? ?? ???? ??? ????? ???? ????? ??? ??? ?????

    ?????? ??? ??? ???? ??? ?????? ?? ????? ????? ????? ??? ??? ????? ???? ????? ?? ???? ???? ??? ???. ???? ??? ?? ?? ? ??? ?????? ?????? ????? ???? ??? ????? ???? ??? ?? ????? ???? ??????? ??????? ???? xenograft tumor ??? ???? ??? ??? ???? ??? ??? ????? (0.41% ???? w/w) ??? ????? ???? ????? ???? ?????? ????? ?????? ?? ????? ???? ??? ? ????? ????? ???? ????? ????? ??????? ???? ????? ??? ????? ????? ?? ????? ?????? ??????? ????? ????? ???? ???? ??? ???? ??????6 ????? ????? 5hmC ????? ?? ????? ???? ?? ????? ??????? ????? ????? ????? ???-???? ???? ???? ????? ? PARP ????? ????? ????? ???? ??? ????. ????? ???? ????? ????? ?? PARP inhibitor talazoparib ???? ???-??? ????? ????? ??? ?????? ?? ?? ? ???? ????? ????? ???? ?????? ???? ??????? ???? ?

    ??????? ??? ???????? HDAC6 in primates ????? ???? ?? ??? ???? ??? ????? ???? ????? ????? ???? ???? ???? ??? ???? ????? ???? ??? ??? ??? ??????? ???? ??? ???? ??? ?? ?????

    ?????? ?? ??? ?????? ????? ?????? ?????? ???? ?? ????? ????? ??????? ???? ???????? ??? ?? ?????? ????? ???? ??? ?????? ??????? ??????? ???? ?? ???? ?????? ????? ?? ? PARP ???? ???? ????? ???? ??? ??? ????? ??? ?? ??? ?????? ???????