Lamin B1 sequesters 53BP1 to control its recruitment to DNA damage

被引：26

作者：

Etourneaud, Laure ^{[1
,2
,3
]}

Moussa, Angela ^{[1
,2
,3
]}

Rass, Emilie ^{[1
,2
,3
]}

Genet, Diane ^{[1
,2
,3
]}

Willaume, Simon ^{[1
,2
,3
]}

Chabance-Okumura, Caroline ^{[1
,2
,3
]}

Wanschoor, Paul ^{[1
,2
,3
]}

Picotto, Julien ^{[1
,2
,3
]}

Theze, Benoit ^{[1
,2
,3
]}

Depagne, Jordane ^{[4
]}

Veaute, Xavier ^{[4
]}

Dizet, Elea ^{[4
]}

Busso, Didier ^{[4
]}

Barascu, Aurelia ^{[1
,2
,3
]}

Irbah, Lamya ^{[1
,2
,5
]}

Kortulewski, Thierry ^{[1
,2
,6
]}

Campalans, Anna ^{[1
,7
]}

Le Chalony, Catherine ^{[1
,2
,3
]}

Zinn-Justin, Sophie ^{[8
]}

Scully, Ralph ^{[9
,10
]}

Pennarun, Gaelle ^{[1
,2
,3
]}

Bertrand, Pascale ^{[1
,2
,3
]}

机构：

[1] Univ Paris, F-92265 Fontenay Aux Roses, France

[2] Univ Paris Saclay, INSERM, iRCM IBFJ, CEA,UMR Stabilite Genet Cellules Souches & Radiat, F-92265 Fontenay Aux Roses, France

[3] CEA, DRF, iRCM IBFJ, DNA Repair & Ageing Team, Fontenay Aux Roses, France

[4] CEA, DRF, iRCM, Genet Engn & Express Platform CIGEX, Fontenay Aux Roses, France

[5] CEA, DRF, iRCM, Imaging Platform, F-92265 Fontenay Aux Roses, France

[6] CEA, DRF, iRCM IBFJ, Radiopathol Team, Fontenay Aux Roses, France

[7] Univ Paris Saclay, iRCM IBFJ, Genet Instabil Res Team, UMR Stabilite Genet Cellules Souches & Radiat,CEA, F-92265 Fontenay Aux Roses, France

[8] Univ Paris Saclay, Inst Integrat Biol Cell I2BC, Lab Struct Biol & Radiobiol, CEA,CNRS, F-91190 Gif Sur Yvette, France

[9] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA

[10] Harvard Med Sch, Boston, MA 02115 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 35期

关键词：

STRAND BREAK REPAIR; NUCLEAR-ENVELOPE; STRUCTURAL BASIS; REGULATES; 53BP1; A-TYPE; RESECTION; PATHWAY; RESPONSES; PRELAMIN; INSTABILITY;

D O I：

10.1126/sciadv.abb3799

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Double-strand breaks (DSBs) are harmful lesions and a major cause of genome instability. Studies have suggested a link between the nuclear envelope and the DNA damage response. Here, we show that lamin B1, a major component of the nuclear envelope, interacts directly with 53BP1 protein, which plays a pivotal role in the DSB repair. This interaction is dissociated after DNA damage. Lamin B1 overexpression impedes 53BP1 recruitment to DNA damage sites and leads to a persistence of DNA damage, a defect in nonhomologous end joining and an increased sensitivity to DSBs. The identification of interactions domains between lamin B1 and 53BP1 allows us to demonstrate that the defect of 53BP1 recruitment and the DSB persistence upon lamin B1 overexpression are due to sequestration of 53BP1 by lamin B1. This study highlights lamin B1 as a factor controlling the recruitment of 53BP1 to DNA damage sites upon injury.

引用

页数：18

共 73 条

[1] The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks [J].