4.6 Article

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

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2013.05.072

Keywords

DNA replication; Smu1; DNA damage; Checkpoint

Funding

  1. Ministry of Science and Technology of China [2011CB966200, 2013CB911000]
  2. National Natural Science Foundation of China [30970950, 81071362, 31171319]
  3. Program for New Century Excellent Talents in University of Ministry of Education of China [NCET-10-0566]
  4. Department of Science and Technology of Sichuan Province [2011SZ0002, 2012JQ0005]
  5. Beauru of Science and Technology of Chengdu [11PPYB072SF]

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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. (C) 2013 Elsevier Inc. All rights reserved.

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