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Nucleic Acids Research, 2000, Vol. 28, No. 14 2847-2854
© 2000 Oxford University Press

The human RAD18 gene product interacts with HHR6A and HHR6B

Hua Xin, Wensheng Lin, Wasana Sumanasekera, Yanbin Zhang, Xiaohua Wu and Zhigang Wang*

306 Health Sciences Research Building, Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA

During DNA replication, lesion bypass is an important cellular response to unrepaired damage in the genome. In the yeast Saccharomyces cerevisiae, Rad6 and Rad18 are required for both the error-free and error-prone lesion bypass mechanisms. Furthermore, Rad6–Rad18 interaction is thought to be critical at an early step during lesion bypass in yeast. Two closely related human homologs of yeast Rad6 have been identified as HHR6A and HHR6B. Here, we report a full-length cDNA coding for the human homolog of yeast Rad18. The human RAD18 gene codes for a protein of 484 amino acid residues with a calculated molecular weight of 54 804 Da, and the gene is localized to chromosome 3 between reference intervals D3S3591 and D3S1283. Human RAD18 protein (hRAD18) was found to interact with HHR6A and HHR6B. When co-expressed in yeast cells, stable hRAD18–HHR6A and hRAD18–HHR6B protein complexes were identified and purified to near homogeneity. Thus, through interaction and complex formation with HHR6A and HHR6B, RAD18 protein may play an important role in lesion bypass mech­anisms in humans. Consistent with its role as a fundamental lesion bypass protein, the RAD18 gene is ubiquitously expressed in various human tissues.

* To whom correspondence should be addressed. Tel: +1 606 323 5784; Fax: +1 606 323 1059; Email: zwang@pop.uky.edu The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors


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