Dealing with DNA Damage in Different Ways

Abstract

In a critical process known as the "DNA damage checkpoint," cells monitor their DNA for damage and halt cell division until the damage has been repaired. Kondo et al. now show that two yeast proteins that function in signaling that DNA damage has occurred actually bind close to the site of damage, but do so in distinct ways. They used a chromatin immunoprecipitation method to detect proteins that bound to a double-stranded break in the DNA resulting from continuous expression of the HO endonuclease. One of the proteins bound, Mec1, belongs to a family of protein kinases that includes the ATM protein mutated in the human disease ataxia telangiectasia. Another protein bound at the site of damage was Ddc1, itself thought to be a DNA-binding protein that may recruit other proteins to a complex formed at the damage site. Recruitment of Ddc1, but not that of Mec1, required the action of another participant in the checkpoint pathway, called Rad24. The results help clarify how cells recognize damaged DNA and then initiate signals that produce the appropriate physiological response.T. Kondo, T. Wakayama, T. Naiki, K. Matsumoto, K. Sugimoto, Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms. Science 294, 867-870 (2001). [Abstract] [Full Text]