The N- and C-termini of Elg1 contribute to the maintenance of genome stability

ELGI (enhanced level of genome instability) encodes a Replication Factor C (RFC) homolog that is important for the maintenance of genome stability. Elgl interacts with Rfc2-5, forming the third alternative RFC complex identified to date. We found that Elgl plays a role in the suppression of spontaneous DNA damage in addition to its previously identified roles in the resistance to DNA damage. Using mutational analysis we examined the function of conserved and unique regions of Elgl in these roles. We found that the Walker A motif in the conserved RFC region is dispensable for Elgl function in vivo. The RFC region is important for association with chromatin although residues predicted to mediate interactions with DNA are dispensable for Elgl function. The unique C-terminus of Elgl mediates oligornerization with Rfc2-5, nuclear import, and chromatin association, and is critical for the function of Elgl. Finally, we demonstrated that the N-terminus of Elgl contributes to the maintenance of genome stability, and that one function of this N-terminus is to promote the nuclear localization of Elgl. Together, these studies delineate the regions of Elgl important for its function in damage resistance and in the suppression of spontaneous DNA damage. (c) 2008 Elsevier B.V All rights reserved.