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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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