Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-49461
Engels, K; Giannattasio, M; Muzi-Falconi, M; Lopes, M; Ferrari, S (2011). 14-3-3 proteins regulate exonuclease 1-dependent processing of stalled replication forks. PLoS Genetics, 7(4):e1001367.
View at publisher
Replication fork integrity, which is essential for the maintenance of genome stability, is monitored by checkpoint-mediated phosphorylation events. 14-3-3 proteins are able to bind phosphorylated proteins and were shown to play an undefined role under DNA replication stress. Exonuclease 1 (Exo1) processes stalled replication forks in checkpoint-defective yeast cells. We now identify 14-3-3 proteins as in vivo interaction partners of Exo1, both in yeast and mammalian cells. Yeast 14-3-3-deficient cells fail to induce Mec1-dependent Exo1 hyperphosphorylation and accumulate Exo1-dependent ssDNA gaps at stalled forks, as revealed by electron microscopy. This leads to persistent checkpoint activation and exacerbated recovery defects. Moreover, using DNA bi-dimensional electrophoresis, we show that 14-3-3 proteins promote fork progression under limiting nucleotide concentrations. We propose that 14-3-3 proteins assist in controlling the phosphorylation status of Exo1 and additional unknown targets, promoting fork progression, stability, and restart in response to DNA replication stress.
88 downloads since deposited on 09 Sep 2011
18 downloads since 12 months
|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|
|Deposited On:||09 Sep 2011 13:30|
|Last Modified:||20 Jul 2014 11:44|
|Publisher:||Public Library of Science|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page