It takes three to the DNA damage response tango

Sapir Schlam-Babayov; Yael Ziv; Yosef Shiloh

doi:10.1080/23723556.2021.1881395

It takes three to the DNA damage response tango

Mol Cell Oncol. 2021 Feb 8;8(2):1881395. doi: 10.1080/23723556.2021.1881395. eCollection 2021.

Authors

Sapir Schlam-Babayov¹, Yael Ziv¹, Yosef Shiloh¹

Affiliation

¹ The David and Inez Myers Laboratory of Cancer Genetics, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University School of Medicine, Tel Aviv, Israel.

Abstract

The DNA damage response is robustly activated by DNA double-strand breaks and controlled by three apical protein kinases of the PI3-kinase-related protein kinase (PIKK) family: ataxia-telangiectasia, mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK). Phosphoproteomic analysis reveals the relative share of these PIKKs in coordinating this network, and compensation by ATR and DNA-PK for ATM absence in the genetic disorder, ataxia-telangiectasia (A-T).

Keywords: ATM; Ataxia-telangiectasia; DNA damage response; PIKKs; phosphoproteomic.

Grants and funding

This work was funded by research grants from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and The Israel Cancer Research Fund (to Yosef Shiloh). Sapir Schlam-Babayov was supported by a Tel Aviv University Global Research and Training Fellowship (GRTF) provided by the Naomi Prawer Kadar Foundation. Work in the group of Ruedi Aebersold was supported by the Swiss National Science Foundation grant 31003A 166435 and by SystemsX.ch, the Swiss Initiative for Systems Biology. Yosef Shiloh is a Research Professor of the Israel Cancer Research Fund.