How do cells sense DNA lesions?

Biochem Soc Trans. 2020 Apr 29;48(2):677-691. doi: 10.1042/BST20191118.

Abstract

DNA is exposed to both endogenous and exogenous DNA damaging agents that chemically modify it. To counteract the deleterious effects exerted by DNA lesions, eukaryotic cells have evolved a network of cellular pathways, termed DNA damage response (DDR). The DDR comprises both mechanisms devoted to repair DNA lesions and signal transduction pathways that sense DNA damage and transduce this information to specific cellular targets. These targets, in turn, impact a wide range of cellular processes including DNA replication, DNA repair and cell cycle transitions. The importance of the DDR is highlighted by the fact that DDR inactivation is commonly found in cancer and causes many different human diseases. The protein kinases ATM and ATR, as well as their budding yeast orthologs Tel1 and Mec1, act as master regulators of the DDR. The initiating events in the DDR entail both DNA lesion recognition and assembly of protein complexes at the damaged DNA sites. Here, we review what is known about the early steps of the DDR.

Keywords: ATM; ATR; DNA damage response; DNA recombination; DNA repair; single-stranded DNA.

Publication types

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

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Cell Cycle
  • DNA / analysis*
  • DNA Damage*
  • DNA Repair
  • DNA Replication
  • DNA, Single-Stranded / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-ets / metabolism
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces
  • Signal Transduction
  • Xenopus laevis

Substances

  • DNA, Single-Stranded
  • ETS translocation variant 6 protein
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae