부산대학교 도서관

DNA polymerase eta (Poln) is a unique translesion DNA synthesis (TLS) enzyme required for the error-free bypass of ultraviolet ray (UV)-induced cyclobutane pyrimidine dimers in DNA. Therefore, its deficiency confers cellular sensitivity to UV radiation and an increased rate of UV-induced mutagenesis. Poln possesses a ubiquitin-binding zinc finger (ubz) domain and a PCNA-interacting-protein (pip) motif in the carboxyterminal region. The role of the Poln pip motif in PCNA interaction required for DNA polymerase recruitment to the stalled replication fork has been demonstrated in earlier studies; however, the function of the ubz domain remains divisive. As per the current notion, the ubz domain of Poln binds to the ubiquitin moiety of the ubiquitinated PCNA, but such interaction is found to be nonessential for Poln's function. In this study, through amino acid sequence alignments, we identify three classes of Poln among different species based on the presence or absence of pip motif or ubz domain and using comprehensive mutational analyses, we show that the ubz domain of Poln, which intrinsically lacks the pip motif directly binds to the interdomain connecting loop (IDCL) of PCNA and regulates Poln's TLS activity. We further propose two distinct modes of PCNA interaction mediated either by pip motif or ubz domain in various Poln homologs. When the pip motif or ubz domain of a given Poln binds to the IDCL of PCNA, such interaction becomes essential, whereas the binding of ubz domain to PCNA through ubiquitin is dispensable for Poln's function. [ABSTRACT FROM AUTHOR]