Replication-dependent and -independent Responses of RAD18 to DNA damage in human cells

Satoshi Nakajima, Li Lan, Shin Ichiro Kanno, Noriko Usami, Katsumi Kobayashi, Masahiko Mori, Tadahiro Shiomi, Akira Yasui

    Research output: Contribution to journalArticlepeer-review

    47 Citations (Scopus)

    Abstract

    Postreplication repair facilitates tolerance of DNA damage during replication, overcoming termination of replication at sites of DNA damage. A major post-replication repair pathway in mammalian cells is translesion synthesis, which is carried out by specialized polymerase(s), such as polymerase η, and is identified by focus formation by the polymerase after irradiation with UVC light. The formation of these foci depends on RAD18, which ubiquitinates PCNA for the exchange of polymerases. To understand the initial processes in translesion synthesis, we have here analyzed the response to damage of RAD18 in human cells. We find that human RAD18 accumulates very rapidly and remains for a long period of time at sites of different types of DNA damage, including UVC light-induced lesions, and x-ray microbeam- and laser-induced single-strand breaks, in a cell cycle-independent manner. The accumulation of RAD18 at DNA damage is observed even when DNA replication is inhibited, and a small region containing a zinc finger motif located in the middle of RAD18 is essential and sufficient for the replication-independent damage accumulation. The zinc finger motif of RAD18 is not necessary for UV-induced polymerase η focus formation, but another SAP (SAF-A/B, Acinus and PIAS) motif near the zinc finger is required. These data indicate that RAD18 responds to DNA damage in two distinct ways, one replication-dependent and one replication-independent, involving the SAP and zinc finger motifs, respectively.

    Original languageEnglish
    Pages (from-to)34687-34695
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume281
    Issue number45
    DOIs
    Publication statusPublished - 2006 Nov 10

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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