A function for ataxia telangiectasia and Rad3-related (ATR) kinase in cytokinetic abscission

Abstract

SummaryAbscission, the final stage of cytokinesis, occurs when the cytoplasmic canal connecting two emerging daughter cells is severed either side of a large proteinaceous structure, the midbody. Here, we expand the functions of ATR to include a cell-cycle-specific role in abscission, which is required for genome stability. All previously characterized roles for ATR depend upon its recruitment to replication protein A (RPA)-coated single-stranded DNA (ssDNA). However, we establish that in each cell cycle ATR, as well as ATRIP, localize to the midbody specifically during late cytokinesis and independently of RPA or detectable ssDNA. Rather, midbody localization and ATR-dependent regulation of abscission requires the known abscission regulator-charged multivesicular body protein 4C (CHMP4C). Intriguingly, this regulation is also dependent upon the CDC7 kinase and the known ATR activator ETAA1. We propose that in addition to its known RPA-ssDNA-dependent functions, ATR has further functions in preventing premature abscission.