Nucleic Acids Research Advance Access originally published online on December 7, 2006
Nucleic Acids Research 2007 35(2):e9; doi:10.1093/nar/gkl979
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2007, Vol. 35, No. 2 e9
© 2006 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Methods Online |
Human RAD18 is involved in S phase-specific single-strand break repair without PCNA monoubiquitination
1 Radgenomics Research Group, Research Center for Charged Particle Therapy Chiba 263-8555, Japan 2 Radiation Effect Mechanisms Research Group, Research Center for Radiation Protection Chiba 263-8555, Japan 3 National Institute of Radiological Sciences Chiba 263-8555, Japan 4 Department of Regulation Biology, Faculty of Science, Saitama University Saitama 338-8570, Japan 5 Institute of Molecular Embryogenesis and Genetics, Kumamoto University Kumamoto 862-0976, Japan
*To whom correspondence should be addressed. Tel: +81 43 206 3136; Fax: +81 43 251 9818; Email: shiomita{at}nirs.go.jp
Received September 25, 2006. Revised October 25, 2006. Accepted October 26, 2006.
Switching from a replicative to a translesion polymerase is an important step to further continue on replication at the site of DNA lesion. Recently, RAD18 (a ubiquitin ligase) was shown to monoubiquitinate proliferating cell nuclear antigen (PCNA) in cooperation with RAD6 (a ubiquitin-conjugating enzyme) at the replication-stalled sites, causing the polymerase switch. Analyzing RAD18-knockout (RAD18–/–) cells generated from human HCT116 cells, in addition to the polymerase switch, we found a new function of RAD18 for S phase-specific DNA single-strand break repair (SSBR). Unlike the case with polymerase switching, PCNA monoubiquitination was not necessary for the SSBR. When compared with wild-type HCT116 cells, RAD18–/– cells, defective in the repair of X-ray-induced chromosomal aberrations, were significantly hypersensitive to X-ray-irradiation and also to the topoisomerase I inhibitor camptothecin (CPT) capable of inducing single-strand breaks but were not so sensitive to the topoisomerase II inhibitor etoposide capable of inducing double-strand breaks. However, such hypersensitivity to CPT observed with RAD18–/– cells was limited to only the S phase due to the absence of the RAD18 S phase-specific function. Furthermore, the defective SSBR observed in S phase of RAD18–/– cells was also demonstrated by alkaline comet assay.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Watanabe, K. Iwabuchi, J. Sun, Y. Tsuji, T. Tani, K. Tokunaga, T. Date, M. Hashimoto, M. Yamaizumi, and S. Tateishi RAD18 promotes DNA double-strand break repair during G1 phase through chromatin retention of 53BP1 Nucleic Acids Res., April 1, 2009; 37(7): 2176 - 2193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Iiizumi, A. Kurosawa, S. So, Y. Ishii, Y. Chikaraishi, A. Ishii, H. Koyama, and N. Adachi Impact of non-homologous end-joining deficiency on random and targeted DNA integration: implications for gene targeting Nucleic Acids Res., November 1, 2008; 36(19): 6333 - 6342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Niimi, S. Brown, S. Sabbioneda, P. L. Kannouche, A. Scott, A. Yasui, C. M. Green, and A. R. Lehmann Regulation of proliferating cell nuclear antigen ubiquitination in mammalian cells PNAS, October 21, 2008; 105(42): 16125 - 16130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Notenboom, R. G. Hibbert, S. E. van Rossum-Fikkert, J. V. Olsen, M. Mann, and T. K. Sixma Functional characterization of Rad18 domains for Rad6, ubiquitin, DNA binding and PCNA modification Nucleic Acids Res., September 27, 2007; 35(17): 5819 - 5830. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Bish and M. P. Myers Werner Helicase-interacting Protein 1 Binds Polyubiquitin via Its Zinc Finger Domain J. Biol. Chem., August 10, 2007; 282(32): 23184 - 23193. [Abstract] [Full Text] [PDF]
|
|