??????? ???????? ?? ???????? ???????? ?????????? ??????? ???? ??????? ???????? ????? ??? ??? ?????? ???????? ?????? ???? ?????????? ???????? ???????? ?????? ?? ??????? ???????????.

?????? ?? ????? ???? ??????? ???????? ?? ??????? ??????? ??????? ??????????? ????????. ????? ????? ????? ??????? ????? ????? ????? ??????? ???????? ????????? ???????? ????? ????? ???? ????? ???????? ?????? ????? ???????.

????? ?????? ??????? ???????? ???????? ???????? ?????? ???????? ??????? ???????? ??????? ???????? ?????????. ????? ?? ???? ??????? ?????? ???????? ??????? ????? ??????? ???????? ????? ?????? ??????? ?? ??????? ??????? ???????? ?? ???????. ???? ???????? ???????? ????? ??????? ??????? ????? ???????? ????? ????? ?? ????? ???????? ??????? ?????? ????? ????? ????. ??? ???? ?? ???? ???? ?????? ??????? ?????? ???????? ??? ?????.

?? 20 ?????? 2024? ??? ???? ???? ???? ?? ???? ???? ?????? ?????? / ?????? ????? ?????? ?????? ???? ????? ?????? "HDAC6 ?????? ?????? ???? ????? ?????? ?????? ??? ????? ??????" ?? ???? Nature.

???? ??? ??????? ???????? ?????? ????? ????????? ??? ??? ?????? ??????? HDAC6? ????? ?? ?????? ??????? ???? ???? ??? ????? ??????? ??? ???????? ?????? ?? HDAC6? ???????? ????? ???? TET2 ?????? ??? ?? ????? ??????.

?? ?????? ???????? ?? ???? ????????? ??? ????? ??? ?????????? ??? ??? ?????? ??????? ?????? ?? ?????? HDAC6 ??? ????????? ????? ??? ???? ?????? ???? ?? ?????????? ????? ????? ????? ???????? (SE14)? ??????? ???? ??????? ?? ?????. ????? ????? ????? ?????? ????? ????? ??????? ?? ??????? ?? ????? ??? ?????? PARP ?? ?????? ??? ????? ???????.

???? ??? ??????? ?? ???? ????? ???? ?? ?????? ??????? ??????? ??? ????? ??? ????? ?????? ?? ???? ??????? ??????? ?????? ?????????? ????? ????? ????? ???????? ???? ????? ???? ???????? ?? ?????? PARP.

????? ????? ??????? ??????? ???????? ???? ??? ????? ??? ??????? ???????? ?? ??? ?????? ??? ???????? ?? ????? ??????? ???????? ???? ?????? ??????? ?????????? ???? ???? ????? ??????? ???????????.

?? ??? ?????? ???? ????? ??? ???????? ??? ???????? ?? ??????? ????? ??????? ?????????? ?????? ??????? ???????? ????? ??? ??? ?? ??????? ??????? ??? ????? ??? ??? ????? ????????? ??? ??????? ?????? ??? ??????? ?????????.

??? ???????? ??? ???????? ??? ??????? ????? ??????? ????? ?????? ???????? (VARS) ????????? ???? ????? ??? ???????? HDAC6 ???? ?????? ???? ????????-D ??????? ?? 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. ?? ??????? ??? ???? ?????? ????????? ?? ??? ????? ????? ?????? ????? ??????? ??? ?????????? ???????? (TDG) ????? ????? ?? ??? ????? ?????? ??????? ?? ????????? ??????. ???? ????? TET2 ChIP-Seq ?? ????? ??????? ????? ????????? END-Seq ?ddC S1 END-Seq? ?????? ??? ?? ??? ??????? ????? ??? ????? ??????. ??? ?? ??? ????? ?????? ?????? ?? ??? ??????? ????? ??? ??? ????? ??????? ?????? ?? ??????? ????? ????? ????????? (5fC/5caC) ?????? TDG.

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

???? ????? ?????? ??????? ?? ??????? ??? ??????? ???????? ?????????? ?????????? ?????? ?????? ????? ????? ?????? ?? ???????? ??? ?? ??? ???????. ?????? ??? ??????? ?? ??????? ???? ?? ???? ??? ????? ??????? ??? ???? ???????? ??????? ???? ???? ??? ??? ????? ??????? ???? ????? ?? ???? ???????. ?? ????? ??? ????? ??????? ?????????? ??? ????? ???? ????? ????? ???? ???????? (0.41% ?????? ???/???) ??? ????? ??? ????? ???? ???? ?? ???? ?????? ???. ??? ?? ?? ??????? ??????? ???????? ???? ???????? ????? ?? ?????? ??????? ?????? ???????? ???? ????? ????? ?????? ???????? ????? PDX ?????? ??????? ?????????. ?? ????? ?????? ????? ?????? ??????? ??????? ???? ?????? ?????? ???????? HDAC6 ???????? ???????? 5hmC? ???? ????? ??????. ?????? ??? ????? ??? ????? ?????? ?? ???? ???? ???????? ??? ?????? ??????? ??? ????? ????? ?????? ???????? ?????? PARP. ??? ???????? ?? ????? ??? ?????? ??????? ?????? ???????? ????? PARP ??????????? ??? ???? ???? ??????? ?????? ???????? ??? ???? ?????? ????? ??? ?????? ?????? ?? ???? ??????? ?? ???? ????? ??? ????? ??????.

??? ??????? ???? ??????? ?? HDAC6 ?? ????????? ?? ?????? ??????? ??????? ???? ????? ?? ????? ????????? ?????????? ??? ???? ?? ?????????? ?? ??????? ??????? ??? ??????? ????????? ??? ???? ??? ????? ????? ?????? ????????? ?? ??????? ??????? ????????.

???????? ??? ???? ???? ??? ??????? ????? ??? ???? ????? ??????? ???????? ??????? ?????? ???????? ???????? ??? ??????? ???? ????? ??????? ????? ????? ??????? ?????? ??????? ?? ???????? ???????? ???? ?? ????? ??? ?????? ??????? ?????? ???????? ??????? PARP ???? ???????? ??????????? ????? ????? ???????.