When heat casts a spell on the DNA damage checkpoints

Open Biol. 2014 Mar 12;4(3):140008. doi: 10.1098/rsob.140008.


Peregrine Laziosi (1265-1345), an Italian priest, became the patron saint of cancer patients when the tumour in his left leg miraculously disappeared after he developed a fever. Elevated body temperature can cause tumours to regress and sensitizes cancer cells to agents that break DNA. Why hyperthermia blocks the repair of broken chromosomes by changing the way that the DNA damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) are activated is an unanswered question. This review discusses the current knowledge of how heat affects the ATR-Chk1 and ATM-Chk2 kinase networks, and provides a possible explanation of why homeothermal organisms such as humans still possess this ancient heat response.

Keywords: ATM; ATR; Chk1; Chk2; DNA damage checkpoint; hyperthermia.

Publication types

  • Review

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Checkpoint Kinase 1
  • Checkpoint Kinase 2 / metabolism
  • Chromosomes / metabolism
  • DNA Damage*
  • Histones / metabolism
  • Humans
  • Protein Kinases / metabolism
  • Reactive Oxygen Species / metabolism
  • Temperature


  • Histones
  • Reactive Oxygen Species
  • Protein Kinases
  • Checkpoint Kinase 2
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK1 protein, human
  • Checkpoint Kinase 1