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    2024-11-22

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

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

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

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

    ???? 20 ????????? 2024, ?????? ????? ? ?????????? ??? ????????? ????????????? ???? ??? ?????????? / 10 ???????????? ?????? ? ??????????? ????? ?? ???????? ???????? ?????????? "???????? HDAC6 ?????? ???????? ???? ?? ???????? ???? ??????" ??? ??? ???????? ??????.

    ??? ?????? ??????????? ?? ??????? ????????-????????? ??????, ????? ????????????? HDAC6, ??? ???????? ?? ????????? ??????????? ???? ????? ???????? ??????????? ???? ?? ?????? ????????????????? ??? HDAC6, ?????? ?????????? TET2 ???????? ??? ???????? ???? ??????.

    ?????????????, ??? ??????? ??????????? ??? ?????? ????? ?????????, ??? ???????? ??????????? ?????????? ???????? ??? ????????? HDAC6 ????? ?? ????????? ??????-????? ??????????-????????????? (SE14) ????????? ???? ??? ?????? ???????? ??? ???? ??? ????. ??? ???????? ??? ???????? ????????????, ????? ???????? ??????????? ????? ???????????? ??? ????PARP ??????????? ????? ?????????? ???????? ???????? ??????.

    ??? ?????? ??????? ?? ??????? ??????????? ???? ????? ???????????? ???? ?????????? ???? ?????? ???? ??????????? ???????????????, ??? ??????? ?? ??????? ?????????? ????? ???????? ???????????? ??? ????????-?????????? ????? ????????? ??? PARP ???????????.

    1

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

    ??? ??? ?? ?????????????? ???????????? ????????-???????? ??????????, ?????????????? ???????? ???????? ????? ?????? ????? ???????????????????????? ?????????????? ????????? ??? ????? ??????????????, ??? ?????????? ??????? ??? ????????-???????? ?????????? ??? ??????????? ???? ??????? ?????????.

    ?? ?????? ??????? ??? ??? ???????? ?? ?? ???????? ??????? ????? ???????????? (VARS), ?? ????????????? HDAC6 ??? ?? ??????? ?-???????? ???????? ???????????? ????????? ??? VARS. ?? ?????? ???? ????????? ??? HDAC6 ????? ????? ????? ???????? ??? ?? ?????? ??? Kd ≈ 2μM ???? ?????????? ???????? ??????????????, ???????????? ??????????? ????????????? (ITC) ?????????????? ??? ??????? ????? ??????????????. ?? ?????????? ??? ?? ????????????? ??????????????? ??? ??????? ??????? ???????? ???? ??????? ?????????? ??? ????? ?? ???????? ?????????? ?? ??????????? ??????????? ??? ?? ???????? ??? ??????? ????? ??? ?????? ???? ????. ???? ???????????? ?? ???????? ?????????????? ??? ???????? ????????????, ?? ?????? ??????? ??? HDAC6 ???????? ?? ??????????? ????????? ??? ????? ???? ??? ???????? ??? ????? ???????? ?? ??????? ????????? ???????????????. ??? ????????, ??? HDAC6 ???????? ????, ?? ???????? ??? mTOR ?????????? ????????? ???? ???????? ??????????? ??? ???? ???????? ??????? ??? ?? ????????? ??????, ????????????? ??? ?? ???????? ??? ??????? ??? ?? ???????????? ??????? ????? ??????? ????.

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

    ??????? ???? ?? ????? ??? HDAC6 ????? ?????? ???????? ???? ???? SE14 ????, ?? ?????? ?????????????? ??? ?????????? ??? ?? ???????? ?????????? ??? HDAC6 ??? ???????? ??? ?????? ????? ???????? ??? ??????? ???? ?? ??? ??? ???????? ??? ???? ??????????. ???? ?? ????? ??? ???????????????? ??? ????????? ??? ?????????? ????? ?? ??????? ????? ??? ???? SE14 ???? ??? ?? ?????????????? ????????? ??? HDAC6, ?? ?????? ??????? ??? ??????????????? ???????? ?????????? ????? ???????? HDAC6 ????????????????? ?? ?? ????. ?? ??????? ?????? ????? (DAC1 ??? DAC2) ?????? ?? ?? ??????? ????? (CD ????) ??? ?? ???? ??????????????????? TET2, ????????????? ?? ???????????????? ??? TET2 ??? ??????????? ???? ?????? ????????. ??? ???????????? ??????? ????? ??? WGBS, ACE-Seq ??? MAB-Seq, ??? ???? ????????? ??? ??????????????? ???????? ?????? ????? ?????? ??????? ???? ??????????????? ???? ?? HDAC6-TET2 ??????? ????. ??? ?????, ?? ?????????? ??? Andre Nussenzweig ???????? ??? ??????? ???? ?????????????? (TDG) ???????? ??????? ???? ??????????????? ????????? ??? ???? ????-????? ?????? ???? ?????????? ?????????. ???? ??????????? TET2 ChIP-Seq ??? ????-???????? ???????????? ???????????? END-Seq ??? ddC S1 END-Seq, ??? ??????? ??? ???????? ?????????? ?????????? ???? ??????. ?? ???? ?????? ?????? ???? ???????? ?????????? ??? ???? ???????? ???? ?? ???? ????? ?????? ??????? ???? TDG ?????????? ??? ??????????????????? (5fC/5caC).


    ????????, ?? ?????? ??????????? ??????? ???????? ???????? ??? ????? ?? ?????? ???? ???????? ?? ??????????? ??????????? ???? ????? ???????? ?????? ?? ?????????? ??? ???? ?????? ???? ?? HDAC6-TET2-TDG ?????????? ????, ?????? ?? ????? ?????????? ?? ??? ???????? ??? ?? ??????? ??? ??????????? ????? ???? ??? ??? ???? ?????????.

    ????????? ??????????? ????? ??????????? ??? ??????? ????? ??????????????? ??? ??????? ??? ??????? ?? ?????????????? ?????????? ????? ???? ????????????? ??? ???????????? ??? ???? ??????, ?????????????? ????. ?????? ??? ???????? ??????????????? ????? ???????? ???? ??????, ?? ?????? ???????? ???????????????? ?? ???????? ??????????? ?????? ?? ????? ??? ???? ????????????. ??? ?? ????????????? ???? ???????????? ???????? ??????, ?? ??????? ????????-?????????? ????? (0.41% ????????, ?? / ??) ???????? ?????????? ???????? ?????? ??? ?????????? ????? ?????. ??? ????? ?????????? ??? ???????????? ???????, ?? ?????? ????? ?????????????? ??? ?? ????????-?????????? ????? ??????????? ?????????????? ??? ???????????? ???? ?? ????????????? ???? ????? ??????. ??? ???????? ??????????, ??????? ???????? ??????? ????? ??????? ????????????? ??? ???????? HDAC6 ?????? ??????????????????, 5hmC ??????? ??? ???? ??????. ???? ???????? ???? ?????? ??? ??? ???????????? ?????????, ?? ??? ?????????? ?????? ?? ??????????? ???? ????????? ??? PARP ???????????. ?? ?????? ??????? ??? ?? ???????????? ??? ????????????-?????????? ????? ??? PARP ?????????? ???????????????? ???????? ???????? ?? ??????????? ????????, ????????????? ?????? ????? ????? ?? ????????? ?? ?????? ???? ???? ???????? ???? ??????.

    ??? ?????, ?? ?????? ??????? ??? HDAC6 ??? ????????? ??? ?? ??????? ???????? ??????? ????????? ????? ??? ???????????? ????????, ????????? ??????????? ??? ???????? ??????? ?????? ?????????? ?????, ???????????? ?? ??????? ????? ??? ?????????????????? ?????????? ??? ??????? ????? ???????.

    ??? ????????, ??? ?????? ????????? ?? ????? ??????????? ??? ?? ???????????? ???????? ??? ???????????? ??????????? ????, ??????????? ???????? ??? ???? ??????, ????????? ?? ?????????? ??? ???????????? ??????????? ???? ??? ???? ?????????, ??? ??????? ??? ?? ???????????? ??? ????????????-?????????? ????? ??? PARP ??????????? ????? ???? ???????? ??? ?? ????? ?????????? ????? ???? ????????????.