DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase.

Budding yeast cells suffering a single unrepaired double-strand break (DSB) trigger the Mec1 (ATR)-dependent DNA damage response that causes them to arrest before anaphase for 12-15 h. Here we find that hyperactivation of the cytoplasm-to-vacuole (CVT) autophagy pathway causes the permanent G2/M arrest of cells with a single DSB that is reflected in the nuclear exclusion of both Esp1 and Pds1. Transient relocalization of Pds1 is also seen in wild-type cells lacking vacuolar protease activity after induction of a DSB. Arrest persists even as the DNA damage-dependent phosphorylation of Rad53 diminishes. Permanent arrest can be overcome by blocking autophagy, by deleting the vacuolar protease Prb1, or by driving Esp1 into the nucleus with a SV40 nuclear localization signal. Autophagy in response to DNA damage can be induced in three different ways: by deleting the Golgi-associated retrograde protein complex (GARP), by adding rapamycin, or by overexpression of a dominant ATG13-8SA mutation.

Citation

Farokh Dotiwala, Vinay V Eapen, Jacob C Harrison, Ayelet Arbel-Eden, Vikram Ranade, Satoshi Yoshida, James E Haber. DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase. Proceedings of the National Academy of Sciences of the United States of America. 2013 Jan 02;110(1):E41-9

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PMID: 23169651

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