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Publication : Loss of Smu1 function de-represses DNA replication and over-activates ATR-dependent replication checkpoint.

First Author  Ren L Year  2013
Journal  Biochem Biophys Res Commun Volume  436
Issue  2 Pages  192-8
PubMed ID  23727573 Mgi Jnum  J:203217
Mgi Id  MGI:5525199 Doi  10.1016/j.bbrc.2013.05.072
Citation  Ren L, et al. (2013) Loss of Smu1 function de-represses DNA replication and over-activates ATR-dependent replication checkpoint. Biochem Biophys Res Commun 436(2):192-8
abstractText  Smu1 is an evolutionarily conserved gene that encodes a member of the WD40-repeat protein family. Disruption of Smu1 function leads to multiple cellular defects including chromosomal instability, aberrant DNA replication and alternative RNA splicing events. In this paper, we show that Smu1 is a chromatin-bound protein that functions as a negative regulator of DNA replication. Knockdown of Smu1 gene expression promotes excessive incorporation of dNTP analogue, implicating the acceleration of DNA synthesis. Smu1-silenced cells show an excessive activation of replication checkpoint in response to ultraviolate (UV) or hydroxyurea treatment, indicating that abnormal stimulation of DNA replication leads to instability of genomic structure. Hence, we propose that Smu1 participates in the protection of genomic integrity by negatively regulating the process of DNA synthesis.
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