The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

被引：94

作者：

Sellou, Hafida ^{[1
,3
]}

Lebeaupin, Theo ^{[1
,2
,3
]}

Chapuis, Catherine ^{[1
,2
]}

Smith, Rebecca ^{[2
,3
]}

Hegele, Anna ^{[3
]}

Singh, Hari R. ^{[3
]}

Kozlowski, Marek ^{[3
]}

Bultmann, Sebastian ^{[4
,5
]}

Ladurner, Andreas G. ^{[3
,5
,6
]}

Timinszky, Gyula ^{[1
,3
]}

Huet, Sebastien ^{[1
,2
]}

机构：

[1] Inst Genet Dev Rennes, CNRS, UMR 6290, F-35043 Rennes, France

[2] Univ Rennes 1, Struct Federat Rech Biosit, F-35043 Rennes, France

[3] Ludwig Maximilians Univ Mnchen, Biomed Ctr Munich, Dept Physiol Chem, D-82152 Planegg Martinsried, Germany

[4] Ludwig Maximilians Univ Munchen, Dept Biol II, D-82152 Planegg Martinsried, Germany

[5] Ludwig Maximilians Univ Mnchen, Ctr Integrated Prot Sci Munich CIPSM, Dept Chem & Biochem, D-81377 Munich, Germany

[6] Ludwig Maximilians Univ Mnchen, Biomed Ctr Munich, Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany

来源：

MOLECULAR BIOLOGY OF THE CELL | 2016年 / 27卷 / 24期

关键词：

DOUBLE-STRAND BREAKS; LIVING CELLS; POLY(ADP-RIBOSYL)ATION; NUCLEOSOME; REPAIR; RECRUITMENT; ACTIVATION; GENOME; LINKS; DECONDENSATION;

D O I：

10.1091/mbc.E16-05-0269

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl) ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)-and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD(+)-and ATP-dependent chromatin relaxation upon DNA damage in vivo.

引用

页码：3791 / 3799

页数：9

共 40 条

[1] DNA double-strand breaks promote methylation of histone H3 on lysine 9 and transient formation of repressive chromatin [J].