Unknown

Dataset Information

0

Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and activation.


ABSTRACT: The XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. However, whether and how XPF binding to ERCC1 is regulated has not yet been established. Here, we show that TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF at Lys911 following UV irradiation or treatment with mitomycin C and that this acetylation is required for XPF-ERCC1 complex assembly and subsequent activation. Mechanistically, acetylation of XPF at Lys911 disrupts the Glu907-Lys911 salt bridge, thereby leading to exposure of a previously unidentified second binding site for ERCC1. Accordingly, loss of XPF acetylation impairs the damage-induced XPF-ERCC1 interaction, resulting in defects in both NER and ICL repair. Our results not only reveal a mechanism that regulates XPF-ERCC1 complex assembly and activation, but also provide important insight into the role of TIP60 in the maintenance of genome stability.

SUBMITTER: Wang J 

PROVIDER: S-EPMC7005904 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and activation.

Wang Jiajia J   He Hanqing H   Chen Binbin B   Jiang Guixing G   Cao Liping L   Jiang Haiping H   Zhang Guofei G   Chen Jianxiang J   Huang Jun J   Yang Bing B   Zhou Chun C   Liu Ting T  

Nature communications 20200207 1


The XPF-ERCC1 heterodimer is a structure-specific endonuclease that is essential for nucleotide excision repair (NER) and interstrand crosslink (ICL) repair in mammalian cells. However, whether and how XPF binding to ERCC1 is regulated has not yet been established. Here, we show that TIP60, also known as KAT5, a haplo-insufficient tumor suppressor, directly acetylates XPF at Lys911 following UV irradiation or treatment with mitomycin C and that this acetylation is required for XPF-ERCC1 complex  ...[more]

Similar Datasets

| S-EPMC2519706 | biostudies-literature
| S-EPMC5599718 | biostudies-literature
| S-EPMC2483505 | biostudies-literature
2018-02-14 | GSE103877 | GEO
| S-EPMC5859969 | biostudies-literature
| S-EPMC9582641 | biostudies-literature
| S-EPMC4536458 | biostudies-literature
| S-EPMC5314179 | biostudies-literature
| S-EPMC6411835 | biostudies-literature
| S-EPMC4331052 | biostudies-literature