A DNA damage response pathway controlled by Tel1 and the Mre11 complex

Mol Cell. 2001 Jun;7(6):1255-66. doi: 10.1016/s1097-2765(01)00270-2.

Abstract

We define a DNA damage checkpoint pathway in S. cerevisiae governed by the ATM homolog Tel1 and the Mre11 complex. In mitotic cells, the Tel1-Mre11 complex pathway triggers Rad53 activation and its interaction with Rad9, whereas in meiosis it acts via Rad9 and the Rad53 paralog Mre4/Mek1. Activation of the Tel1-Mre11 complex pathway checkpoint functions appears to depend upon the Mre11 complex as a damage sensor and, at least in meiotic cells, to depend on unprocessed DNA double-strand breaks (DSBs). The DSB repair functions of the Mre11 complex are enhanced by the pathway, suggesting that the complex both initiates and is regulated by the Tel1-dependent DSB signal. These findings demonstrate that the diverse functions of the Mre11 complex in the cellular DNA damage response are conserved in mammals and yeast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Cycle Proteins*
  • Checkpoint Kinase 2
  • DNA Damage / physiology*
  • DNA Repair / physiology
  • DNA-Binding Proteins*
  • Endodeoxyribonucleases*
  • Exodeoxyribonucleases*
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism*
  • Genes, cdc / physiology
  • Intracellular Signaling Peptides and Proteins
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Saccharomyces cerevisiae Proteins*
  • Yeasts

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • RAD50 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • Protein Kinases
  • Checkpoint Kinase 2
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • RAD53 protein, S cerevisiae
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • MRE11 protein, S cerevisiae