Novel insights into the mechanism of cell cycle kinases Mec1(ATR) and Tel1(ATM)

Crit Rev Biochem Mol Biol. 2021 Oct;56(5):441-454. doi: 10.1080/10409238.2021.1925218. Epub 2021 Jun 20.

Abstract

DNA replication is a highly precise process which usually functions in a perfect rhythm with cell cycle progression. However, cells are constantly faced with various kinds of obstacles such as blocks in DNA replication, lack of availability of precursors and improper chromosome alignment. When these problems are not addressed, they may lead to chromosome instability and the accumulation of mutations, and even cell death. Therefore, the cell has developed response mechanisms to keep most of these situations under control. Of the many factors that participate in this DNA damage response, members of the family of phosphatidylinositol 3-kinase-related protein kinases (PIKKs) orchestrate the response landscape. Our understanding of two members of the PIKK family, human ATR (yeast Mec1) and ATM (yeast Tel1), and their associated partner proteins, has shown substantial progress through recent biochemical and structural studies. Emerging structural information of these unique kinases show common features that reveal the mechanism of kinase activity.

Keywords: ATM; ATR; DNA damage response; DNA replication; Mec1; PIKK; Tel1; checkpoint.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Cell Cycle / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA Damage
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Protein Serine-Threonine Kinases* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • MEC1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae