Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34240

El-Shemerly, M; Janscak, P; Hess, D; Jiricny, J; Ferrari, S (2005). Degradation of human exonuclease 1b upon DNA synthesis inhibition. Cancer Research, 65(9):3604-3609.

[img] PDF - Registered users only
326kB

View at publisher

Abstract

In response to DNA damage, signaling pathways are triggered that either block the cell division cycle at defined transitions (G1-S and G2-M) or slow down progression through the S phase. Nucleases play important roles in DNA synthesis, recombination, repair, and apoptosis. In this study, we have examined the regulation of human exonuclease 1 (hEXO1b). The endogenous hEXO1b protein was only detected upon enrichment by immunoprecipitation. We found that hEXO1b was constantly expressed throughout the cell cycle. However, treatment of cells with agents that cause arrest of DNA replication led to rapid degradation of hEXO1b. This effect was fully reversed upon removal of the block. Analysis of synchronized cells showed that degradation of hEXO1b during the S phase was strictly dependent on DNA synthesis inhibition. DNA damage caused by UV-C radiation, ionizing radiation, cisplatin, or the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine did not affect hEXO1b stability. We show that hEXO1b was phosphorylated in response to inhibition of DNA synthesis and that phosphorylation coincided with rapid protein degradation through ubiquitin-proteasome pathways. Our data support the evidence that control of exonuclease 1 activity may be critical for the maintenance of stalled replication forks.

Citations

22 citations in Web of Science®
25 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 09 Jul 2010
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
Language:English
Date:2005
Deposited On:09 Jul 2010 12:31
Last Modified:04 Dec 2013 16:49
Publisher:American Association for Cancer Research
ISSN:0008-5472
Publisher DOI:10.1158/0008-5472.CAN-04-4069
PubMed ID:15867354

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page