When heat casts a spell on the DNA damage checkpoints

Abstract

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 theway that the DNA damage checkpoint kinases ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) are activated is an unanswered question. This reviewdiscusses the current knowledge of howheat 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. © 2014 The Authors.