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Originally published In Press as doi:10.1074/jbc.M004936200 on August 15, 2000

J. Biol. Chem., Vol. 275, Issue 45, 34931-34937, November 10, 2000
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XAB2, a Novel Tetratricopeptide Repeat Protein Involved in Transcription-coupled DNA Repair and Transcription*

Yoshimichi NakatsuDagger §, Hiroshi AsahinaDagger , Elisabetta Citterio, Suzanne Rademakers, Wim Vermeulen, Shinya KamiuchiDagger , Jing-Ping YeoDagger , Min-Cheh KhawDagger , Masafumi SaijoDagger §, Naohiko KodoDagger , Toshiro MatsudaDagger , Jan H. J. Hoeijmakers, and Kiyoji TanakaDagger §||

From the Dagger  Institute for Molecular and Cellular Biology, Osaka University, and § CREST, Japan Science and Technology Corporation (JST), 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan and  MGC-Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus University, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

Nucleotide excision repair is a highly versatile DNA repair system responsible for elimination of a wide variety of lesions from the genome. It is comprised of two subpathways: transcription-coupled repair that accomplishes efficient removal of damage blocking transcription and global genome repair. Recently, the basic mechanism of global genome repair has emerged from biochemical studies. However, little is known about transcription-coupled repair in eukaryotes. Here we report the identification of a novel protein designated XAB2 (XPA-binding protein 2) that was identified by virtue of its ability to interact with XPA, a factor central to both nucleotide excision repair subpathways. The XAB2 protein of 855 amino acids consists mainly of 15 tetratricopeptide repeats. In addition to interacting with XPA, immunoprecipitation experiments demonstrated that a fraction of XAB2 is able to interact with the transcription-coupled repair-specific proteins CSA and CSB as well as RNA polymerase II. Furthermore, antibodies against XAB2 inhibited both transcription-coupled repair and transcription in vivo but not global genome repair when microinjected into living fibroblasts. These results indicate that XAB2 is a novel component involved in transcription-coupled repair and transcription.

* This work has been supported by grants from the Ministry of Education, Science, Sports and Culture of Japan, Health Science Research Grants for Research on Human Genome and Gene Therapy from the Ministry of Health and Welfare of Japan, and CREST, Japan Science and Technology. This research was also supported by Dutch Cancer Society Projects EUR94-763 and 1800, the Dutch Science Foundation, EC contracts, a SPINOZA premium, and the Louis Jeantet Foundation (to J. H. J. H.).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.

The nucleotide sequence reported in this paper has been submitted to the DDBJ/GenBankTM/EBI Data Bank with accession number AB026111.

|| To whom correspondence should be addressed. Tel.: 81-6-6879-7971; Fax: 81-6-6877-9136; E-mail: ktanaka@imcb.osaka-u.ac.jp.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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