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

Elias A. Tannous, Peter M. Burgers

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)441-454
Number of pages14
JournalCritical Reviews in Biochemistry and Molecular Biology
Volume56
Issue number5
DOIs
StatePublished - 2021

Keywords

  • ATM
  • ATR
  • DNA damage response
  • DNA replication
  • Mec1
  • PIKK
  • Tel1
  • checkpoint

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