Essentiality of Ku70/80 in Ustilago maydis is related to its ability to suppress DNA damage signalling at telomeres

Abstract

Ku heterodimer is formed of two subunits Ku70 and Ku80 that bind with high affinity to DNA ends in a sequence independent manner. Ku has a role in several cellular processes including DNA repair, telomere maintenance, transcription and apoptosis. Ku heterodimer is essential in human cells as well as in Ustilago maydis, a well-characterized fungal system used in DNA repair studies. We found that depletion of Ku proteins in U. maydis elicits a DNA damage response (DDR) at telomeres resulting in a permanent cell cycle arrest, which depends on the activation of the Atr1-Chk1 signalling cascade. A consequence of this inappropriate activation is the induction of aberrant homologous recombination at telomeres manifested by the formation of extrachromosomal telomere circles, telomere lengthening and the accumulation of unpaired telomere C-strand. Abrogation of the DDR response by deleting either chk1 or atr1 genes alleviates much of these aberrant recombination process suggesting that one of the roles of Ku proteins at telomeres in Ustilago maydis is related to the suppression of unscheduled DNA damage signalling at telomeres, in addition to the protection of telomeres.