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The initiator caspase Dronc plays a non-apoptotic role in promoting DNA damage signalling in D. melanogaster.

Authors
  • Khan, Chaitali1
  • Muliyil, Sonia1
  • Ayyub, Champakali1
  • Rao, Basuthkar J2
  • 1 Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai 400005, India. , (India)
  • 2 Department of Biological Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai 400005, India [email protected] , (India)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Sep 15, 2017
Volume
130
Issue
18
Pages
2984–2995
Identifiers
DOI: 10.1242/jcs.200782
PMID: 28751499
Source
Medline
Keywords
License
Unknown

Abstract

The phosphorylation of the variant histone H2Ax (denoted γH2Ax; γH2Av in flies) constitutes an important signalling event in DNA damage sensing, ensuring effective repair by recruiting DNA repair machinery. In contrast, the γH2Av response has also been reported in dying cells, where it requires activation of caspase-activated DNases (CADs). Moreover, caspases are known to be required downstream of DNA damage for cell death execution. We show here, for the first time, that the Drosophila initiator caspase Dronc acts as an upstream regulator of the DNA damage response (DDR) independently of executioner caspases by facilitating γH2Av signalling, possibly through a function that is not related to apoptosis. Such a γH2Av response is mediated by ATM rather than ATR, suggesting that Dronc function is required upstream of ATM. In contrast, the role of γH2Av in cell death requires effector caspases and is associated with fragmented nuclei. Our study uncovers a novel function of Dronc in response to DNA damage aimed at promoting DDR via γH2Av signalling in intact nuclei. We propose that Dronc plays a dual role that can either initiate DDR or apoptosis depending upon its level and the required threshold of its activation in damaged cells.This article has an associated First Person interview with the first author of the paper.

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