Domain structure, localization, and function of DNA polymerase η, defective in xeroderma pigmentosum variant cells
- Patricia Kannouche1,
- Bernard C. Broughton1,
- Marcel Volker2,
- Fumio Hanaoka3,
- Leon H.F. Mullenders2, and
- Alan R. Lehmann1,4
- 1MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton BN1 9RR, UK; 2MGC—Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands; 3Institute of Molecular and Cellular Biology, Osaka University, Osaka 565–0871, Japan.
Abstract
DNA polymerase η carries out translesion synthesis past UV photoproducts and is deficient in xeroderma pigmentosum (XP) variants. We report that polη is mostly localized uniformly in the nucleus but is associated with replication foci during S phase. Following treatment of cells with UV irradiation or carcinogens, it accumulates at replication foci stalled at DNA damage. The C-terminal third of polη is not required for polymerase activity. However, the C-terminal 70 aa are needed for nuclear localization and a further 50 aa for relocalization into foci. Polη truncations lacking these domains fail to correct the defects in XP-variant cells. Furthermore, we have identified mutations in two XP variant patients that leave the polymerase motifs intact but cause loss of the localization domains.
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Footnotes
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↵4 Corresponding author.
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E-MAIL a.r.lehmann{at}sussex.ac.uk; FAX 44-1273-678121.
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Article and publication are at www.genesdev.org/cgi/doi/10.1101/gad.187501
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- Received August 10, 2000.
- Accepted November 30, 2000.
- Cold Spring Harbor Laboratory Press
