Dataset Information


14-3-3 Proteins regulate exonuclease 1-dependent processing of stalled replication forks.

ABSTRACT: 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.


PROVIDER: S-EPMC3077382 | BioStudies | 2011-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5919743 | BioStudies
1000-01-01 | S-EPMC5159547 | BioStudies
1000-01-01 | S-EPMC5920239 | BioStudies
2020-01-01 | S-EPMC7102976 | BioStudies
2019-01-01 | S-EPMC6366903 | BioStudies
2018-01-01 | S-EPMC6111017 | BioStudies
2015-01-01 | S-EPMC4298733 | BioStudies
1000-01-01 | S-EPMC4075360 | BioStudies
2020-01-01 | S-EPMC7225081 | BioStudies
2008-01-01 | S-EPMC2258774 | BioStudies