Ddc2 mediates Mec1 activation through a Ddc1- or Dpb11-independent mechanism.

Ddc2 mediates Mec1 activation through a Ddc1- or Dpb11-independent mechanism.

Blog Article

The protein kinase Mec1 (ATR ortholog) and its partner Ddc2 (ATRIP ortholog) play a key role in DNA damage checkpoint responses in budding yeast.Previous studies have established the model in which Ddc1, a subunit of the checkpoint clamp, and Dpb11, related to TopBP1, activate Mec1 directly and control DNA damage checkpoint responses at G1 and G2/M.In back roads clothing this study, we show that Ddc2 contributes to Mec1 activation through a Ddc1- or Dpb11-independent mechanism.

The catalytic activity of Mec1 increases after DNA damage in a Ddc2-dependent manner.In contrast, Mec1 activation occurs even in the absence of Ddc1 and Dpb11 function at G2/M.Ddc2 recruits Mec1 to sites of DNA damage.

To dissect the role of Ddc2 in Mec1 activation, we isolated and characterized a separation-of-function mutation in DDC2, called ddc2-S4.The ddc2-S4 mutation does not affect Mec1 recruitment but diminishes Mec1 activation.Mec1 phosphorylates histone H2A in response to DNA damage.

The ddc2-S4 mutation decreases phosphorylation of histone H2A more significantly than the absence of Ddc1 and Dpb11 function does.Our results suggest that Ddc2 plays a critical role chiefs wine glass in Mec1 activation as well as Mec1 localization at sites of DNA damage.