Structure and function of the apical PIKKs in double-strand break repair.

Abstract

Members of the phosphatidylinositol 3' kinase (PI3K)-related kinases (PIKKs) family, including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), ataxia telangiectasia mutated (ATM), ataxia-telangiectasia mutated and Rad3-related (ATR), mammalian target of rapamycin (mTOR), suppressor with morphological effect on genitalia 1 (SMG1), and transformation/transcription domain-associated protein 1 (TRRAP/Tra1), participate in a variety of physiological processes, such as cell-cycle control, metabolism, transcription, replication, and the DNA damage response. In eukaryotic cells, DNA-PKcs, ATM, and ATR-ATRIP are the main sensors and regulators of DNA double-strand break repair. The purpose of this review is to describe recent structures of DNA-PKcs, ATM, and ATR, as well as their functions in activation and phosphorylation in different DNA repair pathways.

• Authors: Jingfei Xu, Noah Bradley, Yuan He
• Journal: Current opinion in structural biology (Curr Opin Struct Biol) Vol. 82 Pg. 102651 (10 2023) ISSN: 1879-033X [Electronic] England
• PMID: 37437397 (Publication Type: Journal Article, Review, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Protein Serine-Threonine Kinases
• Cell Cycle Proteins
• Tumor Suppressor Proteins
• Ataxia Telangiectasia Mutated Proteins
• DNA

Topics

• Protein Serine-Threonine Kinases (genetics, metabolism)
• Cell Cycle Proteins (genetics, metabolism)
• Tumor Suppressor Proteins (genetics, metabolism)
• Ataxia Telangiectasia Mutated Proteins (genetics)
• Signal Transduction
• DNA Damage
• DNA Repair
• Phosphorylation
• DNA (metabolism)