GTC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Genes to Cells (2004) 9, 1139-1150. doi:10.1111/j.1365-2443.2004.00797.x
© 2004 Blackwell Publishing or its licensors
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kusumoto, R.
Right arrow Articles by Hanaoka, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kusumoto, R.
Right arrow Articles by Hanaoka, F.

DNA binding properties of human DNA polymerase {eta}: implications for fidelity and polymerase switching of translesion synthesis

Rika Kusumoto1,2,a, Chikahide Masutani1, Shizu Shimmyo1,2, Shigenori Iwai3 and Fumio Hanaoka1,4,*

1 Graduate School of Frontier Biosciences, Osaka University, and CREST, Japan Science and Technology Corporation, 1–3 Yamada-oka, Suita, Osaka 565–0871, Japan
2 Graduate School of Pharmaceutical Sciences, Osaka University, 1–6 Yamada-oka, Suita, Osaka 565–0871, Japan
3 Graduate School of Engineering Science, Osaka University, 1–3 Machikaneyama, Toyonaka, Osaka 560–8531, Japan
4 Cellular Physiology Laboratory, RIKEN Discovery Research Institute, Wako-shi, Saitama 351–0198, Japan

The human XPV (xeroderma pigmentosum variant) gene is responsible for the cancer–prone xeroderma pigmentosum syndrome and encodes DNA polymerase {eta} (pol {eta}), which catalyses efficient translesion synthesis past cis-syn cyclobutane thymine dimers (TT dimers) and other lesions. The fidelity of DNA synthesis by pol {eta} on undamaged templates is extremely low, suggesting that pol {eta} activity must be restricted to damaged sites on DNA. Little is known, however, about how the activity of pol {eta} is targeted and restricted to damaged DNA. Here we show that pol {eta} binds template/primer DNAs regardless of the presence of TT dimers. Rather, enhanced binding to template/primer DNAs containing TT dimers is only observed when the 3'-end of the primer is an adenosine residue situated opposite the lesion. When two nucleotides have been incorporated into the primer beyond the TT dimer position, the pol {eta}-template/primer DNA complex is destabilized, allowing DNA synthesis by DNA polymerases {alpha} or {delta} to resume. Our study provides mechanistic explanations for polymerase switching at TT dimer sites.

Communicated by: Hiroyuki Araki

aPresent address: National Institute on Ageing, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA

* Correspondence: E-mail: fhanaoka{at}fbs.osaka-u.ac.jp




This article has been cited by other articles:


Home page
 CarcinogenesisHome page
K. Sugasawa
Xeroderma pigmentosum genes: functions inside and outside DNA repair
Carcinogenesis, March 1, 2008; 29(3): 455 - 465.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
M. S. Yuasa, C. Masutani, A. Hirano, M. A. Cohn, M. Yamaizumi, Y. Nakatani, and F. Hanaoka
A human DNA polymerase eta complex containing Rad18, Rad6 and Rev1; proteomic analysis and targeting of the complex to the chromatin-bound fraction of cells undergoing replication fork arrest.
Genes Cells, July 1, 2006; 11(7): 731 - 744.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q. Lin, A. B. Clark, S. D. McCulloch, T. Yuan, R. T. Bronson, T. A. Kunkel, and R. Kucherlapati
Increased Susceptibility to UV-Induced Skin Carcinogenesis in Polymerase {eta}-deficient Mice
Cancer Res., January 1, 2006; 66(1): 87 - 94.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS
Copyright © 2004 by Wiley-Blackwell Publishing.