Overexpression of the ATR homologous checkpoint kinase Mei-41 induces a G2/M checkpoint in imaginal tissue.

BACKGROUND

DNA damage generally results in the activation of ATM/ATR kinases and the downstream checkpoint kinases Chk1/Chk2. In the ATR homologue ( is pivotal to DNA damage repair and cell cycle checkpoint signalling. Although various mutant alleles have been analyzed in the past, no gain-of-function allele is yet available. To fill this gap, we have generated transgenic flies allowing temporal and tissue-specific induction of

RESULTS

Overexpression of in wing and eye anlagen affects proliferation and a G2/M checkpoint even in the absence of genomic stress. Similar consequences were observed following the overexpression of the downstream kinase Grapes (Grp) but not of Loki (Lok), encoding the respective Chk1 and Chk2 homologues, in agreement with their previously reported activities. Moreover, we show that irradiation induced cell cycle arrest was prolonged in the presence of ectopic expression. Similar to irradiation stress, triggered the occurrence of a slower migrating form of Grp, implying specific phosphorylation of Grp in response to either signal. Using a p53R-GFP biosensor, we further show that overexpression of was sufficient to elicit a robust p53 activation in vivo.

CONCLUSION

We conclude that overexpression of the ATR homologue elicits an effectual DNA damage response irrespective of irradiation.