跳转至内容
Merck
  • SIRT1 regulates DNA damage signaling through the PP4 phosphatase complex.

SIRT1 regulates DNA damage signaling through the PP4 phosphatase complex.

Nucleic acids research (2023-06-13)
George Rasti, Maximilian Becker, Berta N Vazquez, Maria Espinosa-Alcantud, Irene Fernández-Duran, Andrés Gámez-García, Alessandro Ianni, Jessica Gonzalez, Laia Bosch-Presegué, Anna Marazuela-Duque, Anna Guitart-Solanes, Sandra Segura-Bayona, Joan-Josep Bech-Serra, Michael Scher, Lourdes Serrano, Uma Shankavaram, Hediye Erdjument-Bromage, Paul Tempst, Danny Reinberg, Mireia Olivella, Travis H Stracker, Carolina de la Torre, Alejandro Vaquero
摘要

The Sirtuin family of NAD+-dependent enzymes plays an important role in maintaining genome stability upon stress. Several mammalian Sirtuins have been linked directly or indirectly to the regulation of DNA damage during replication through Homologous recombination (HR). The role of one of them, SIRT1, is intriguing as it seems to have a general regulatory role in the DNA damage response (DDR) that has not yet been addressed. SIRT1-deficient cells show impaired DDR reflected in a decrease in repair capacity, increased genome instability and decreased levels of γH2AX. Here we unveil a close functional antagonism between SIRT1 and the PP4 phosphatase multiprotein complex in the regulation of the DDR. Upon DNA damage, SIRT1 interacts specifically with the catalytical subunit PP4c and promotes its inhibition by deacetylating the WH1 domain of the regulatory subunits PP4R3α/β. This in turn regulates γH2AX and RPA2 phosphorylation, two key events in the signaling of DNA damage and repair by HR. We propose a mechanism whereby during stress, SIRT1 signaling ensures a global control of DNA damage signaling through PP4.

材料
货号
品牌
产品描述

Sigma-Aldrich
单克隆抗-FLAG® M2 小鼠抗, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
抗 β-肌动蛋白抗体,小鼠单克隆, clone AC-15, purified from hybridoma cell culture
Sigma-Aldrich
抗-HA 兔抗, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
抗-α-微管蛋白抗体,小鼠单克隆, clone DM1A, purified from hybridoma cell culture
Sigma-Aldrich
抗-Sirt1(Sir2) 抗体, Upstate®, from rabbit
Sigma-Aldrich
Rabbit anti-Phospho RPA32 (S4/S8) Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
Sigma-Aldrich
抗绿色荧光蛋白抗体,仅原始GFP,克隆264-449-2, clone 264-449-2, Chemicon®, from mouse