DSpace university logo mark
Advanced Search
Japanese | English 

NAOSITE : Nagasaki University's Academic Output SITE > School of Medicine > Bulletin > Acta Medica Nagasakiensia > Volume 53, Supplement >

The Maintenance of ATM Dependent G2/M Checkpoint Arrest Following Exposure to Ionizing Radiation

File Description SizeFormat
acta_53_supl_19.pdf69.29 kBAdobe PDFView/Open

Title: The Maintenance of ATM Dependent G2/M Checkpoint Arrest Following Exposure to Ionizing Radiation
Authors: Shibata, Atsushi / Barton, Olivia / Noon T. Angela / Dahm, Kirsten / Deckbar, Dorothee / Goodarzi A. Aaron / Lobrich, Markus / Jeggo A. Penny
Issue Date: Mar-2009
Citation: Acta medica Nagasakiensia, 53(supl.), pp.19-21 ; 2009
Abstract: The G2/M checkpoint is important in preventing cells with unrepaired DNA double strand breaks (DSBs) entering mitosis, an event which is likely to result in genomic instability. We recently reported that checkpoint arrest is maintained until close to completion of DSB repair and that the duration of checkpoint arrest depends on the dose and DSB repair capacity rather than lasting for a fixed period of time. ATM leads to phosphorylation of Chk1/2 in G2 phase following exposure to ionizing radiation. These transducer kinases can phosphorylate and inhibit Cdc25 activity, which is the phosphatase regulating mitotic entry. In this study we dissect three processes that contribute to the maintenance of checkpoint arrest in irradiated G2 phase cells. First, the ATR-Chk1 pathway contributes to maintaining checkpoint arrest, although it is dispensable for the initial activation of checkpoint arrest. Second, ongoing ATM to Chk2 signalling from unrepaired DSBs contributes to checkpoint arrest. This process plays a greater role in a repair defective background. Finally, slow decay of the initially activated Chk2 also contributes to the maintenance of checkpoint arrest. 53BP1 and MDC1 defective cells show an initial checkpoint defect after low doses but are proficient in initial activation of arrest after high doses. After higher radiation doses, however, 53BP1-/- and MDC1-/- MEFs fail to maintain checkpoint arrest. Furthermore 53BP1-/- and MDC1-/- MEFs display elevated mitotic breakage even after high doses. We show that the defect in the maintenance of checkpoint arrest conferred by 53BP1 and MDC1 deficiency substantially enhances chromosome breakage.
Keywords: Cell cycle checkpoints / DNA damage response / ATM signalling / Radiation sensitivity
URI: http://hdl.handle.net/10069/21794
ISSN: 00016055
Relational Links: http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/53.S19
Type: Departmental Bulletin Paper
Text Version: publisher
Appears in Collections:Volume 53, Supplement

Citable URI : http://hdl.handle.net/10069/21794

All items in NAOSITE are protected by copyright, with all rights reserved.


Valid XHTML 1.0! Copyright © 2006-2015 Nagasaki University Library - Feedback Powerd by DSpace