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Originally published In Press as doi:10.1074/jbc.M107696200 on September 25, 2001
J. Biol. Chem., Vol. 276, Issue 48, 44688-44694, November 30, 2001
Cyclobutane Pyrimidine Dimers Are Responsible for the Vast
Majority of Mutations Induced by UVB Irradiation in Mammalian
Cells*
Young-Hyun
You §,
Dong-Hyun
Lee ,
Jung-Hoon
Yoon ,
Satoshi
Nakajima¶,
Akira
Yasui¶, and
Gerd P.
Pfeifer
From the Department of Biology, Beckman Research
Institute of the City of Hope, Duarte, California 91010 and the
¶ Institute of Development, Aging and Cancer, Tohoku University,
Sendai 980-77, Japan
The most prevalent DNA lesions induced by UVB are
the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4)
pyrimidone photoproducts ((6-4)PPs). It has been a long standing
controversy as to which of these photoproduct is responsible for
mutations in mammalian cells. Here we have introduced
photoproduct-specific DNA photolyases into a mouse cell line carrying
the transgenic mutation reporter genes lacI and
cII. Exposure of the photolyase-expressing cell lines to
photoreactivating light resulted in almost complete repair of either
CPDs or (6-4)PPs within less than 3 h. The mutations produced by
the remaining, nonrepaired photoproducts were scored. The mutant
frequency in the cII gene after photoreactivation by CPD
photolyase was reduced from 127 × 10 5 to 34 × 10 5 (background, 8-10 × 10 5).
Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant
frequency after photoreactivation repair of CPDs was reduced from
148 × 10 5 to 28 × 10 5
(background, 6-10 × 10 5). Mutation spectra
obtained with and without photoreactivation by CPD photolyase indicated
that the remaining mutations were derived from background mutations,
unrepaired CPDs, and other DNA photopoducts including perhaps a small
contribution from (6-4)PPs. We conclude that CPDs are responsible for
at least 80% of the UVB-induced mutations in this mammalian cell model.
*
This work was supported by Grant ES06070 from the NIEHS,
National Institutes of Health (to G. P. P.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
Present address: Lawrence Berkeley National Laboratory, Berkeley,
CA 94720.
To whom correspondence should be addressed. Tel.:
626-301-8853; Fax: 626-930-5366; E-mail: gpfeifer@coh.org.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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