Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair.
Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair.
复制标题
DOI：
10.1093/nar/gkab019
复制
发表时间：
2021-02-26
影响因子：
14.9
通讯作者：
Cristea IM
中科院分区：
文献类型：
--
作者：
Murray-Nerger LA;Justice JL;Rekapalli P;Hutton JE;Cristea IM
核层的完整性和调控对核组织和染色质稳定性至关重要，其失调与层状病变和癌症有关。虽然许多翻译后修饰已经在层蛋白上被发现，但很少被认为具有调节功能。在这里，我们确定在K134位点的层粘胶蛋白B1 （LMNB1）乙酰化是一个控制核外周稳定性、细胞周期进程和DNA修复的分子开关。LMNB1乙酰化可防止1型疱疹病毒（HSV-1）感染期间的膜破坏，从而抑制病毒产生。我们还证明了该位点对未感染细胞层流过程的广泛影响。LMNB1乙酰化通过损害53BP1对受损DNA的招募来负性调节规范的非同源末端连接。这种缺陷导致DNA损伤解决的延迟和G1/S检查点的持续激活。总之，我们揭示了LMNB1乙酰化是控制DNA修复途径选择和稳定核外周的机制。
The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.
登录
查看更多内容
影响因子：
56.9
作者：
Choudhary, Chunaram;Kumar, Chanchal;Mann, Matthias
通讯作者：
Mann, Matthias
DOI：
10.1126/science.aaf5573
发表时间：
2016-08-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Abudayyeh OO;Gootenberg JS;Konermann S;Joung J;Slaymaker IM;Cox DB;Shmakov S;Makarova KS;Semenova E;Minakhin L;Severinov K;Regev A;Lander ES;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
3.7
作者：
Bresnahan, WA;Boldogh, I;Albrecht, T
通讯作者：
Albrecht, T
影响因子：
2.7
作者：
Davison, Andrew J.;Eberle, Richard;Ehlers, Bernhard;Hayward, Gary S.;McGeoch, Duncan J.;Minson, Anthony C.;Pellett, Philip E.;Roizman, Bernard;Studdert, Michael J.;Thiry, Etienne
通讯作者：
Thiry, Etienne