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

作者：Yuasa MS; Masutani C; Hirano A; Cohn MA; Yamaizumi M; Nakatani Y; Hanaoka F^*

来源：Genes to Cells, 2006, 11(7): 731-744.

DOI：10.1111/j.1365-2443.2006.00974.x

DNA polymerase eta (Pol eta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. Loss of human Pol eta leads to xeroderma pigmentosum variant syndrome, clearly indicating that Pol eta plays a vital role in preventing skin cancer caused by exposure to sunlight. To further examine Pol eta functions and the mechanisms that regulate this important protein, Pol eta complexes were purified from HeLa cells over-expressing epitope-tagged Pol eta, and polypeptides associated with Pol eta, including Rad18, Rad6 and Rev1, were identified by a combination of mass spectrometry and Western blot analysis. The chromatin-bound fractions of cells subjected to UV irradiation, S phase synchronization, or S phase arrest were specifically enriched in such complexes. These results suggest that arrested replication forks strengthen interactions among Pol eta, Rad18/Rad6 and Rev1, consistent with the requirement for effective TLS by Pol eta at sites of DNA lesions.

• 出版日期2006-7