Davidson Marta B, Brown Grant W
Department of Biochemistry and Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada.
DNA Repair (Amst). 2008 Aug 2;7(8):1221-32. doi: 10.1016/j.dnarep.2008.04.001. Epub 2008 May 14.
ELG1 (enhanced level of genome instability) encodes a Replication Factor C (RFC) homolog that is important for the maintenance of genome stability. Elg1 interacts with Rfc2-5, forming the third alternative RFC complex identified to date. We found that Elg1 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 Elg1 in these roles. We found that the Walker A motif in the conserved RFC region is dispensable for Elg1 function in vivo. The RFC region is important for association with chromatin although residues predicted to mediate interactions with DNA are dispensable for Elg1 function. The unique C-terminus of Elg1 mediates oligomerization with Rfc2-5, nuclear import, and chromatin association, and is critical for the function of Elg1. Finally, we demonstrated that the N-terminus of Elg1 contributes to the maintenance of genome stability, and that one function of this N-terminus is to promote the nuclear localization of Elg1. Together, these studies delineate the regions of Elg1 important for its function in damage resistance and in the suppression of spontaneous DNA damage.
ELG1(增强的基因组不稳定性水平)编码一种复制因子C(RFC)同源物,对维持基因组稳定性很重要。Elg1与Rfc2 - 5相互作用,形成了迄今为止鉴定出的第三种替代RFC复合物。我们发现,Elg1除了在先前确定的对DNA损伤的抗性中发挥作用外,还在抑制自发DNA损伤中发挥作用。我们使用突变分析研究了Elg1保守区域和独特区域在这些作用中的功能。我们发现,保守的RFC区域中的沃克A基序对于Elg1在体内的功能是可有可无的。RFC区域对于与染色质的结合很重要,尽管预测介导与DNA相互作用的残基对于Elg1的功能是可有可无的。Elg1独特的C末端介导与Rfc2 - 5的寡聚化、核输入和染色质结合,并且对Elg1的功能至关重要。最后,我们证明了Elg1的N末端有助于维持基因组稳定性,并且该N末端的一个功能是促进Elg1的核定位。总之,这些研究描绘了Elg1在抗损伤和抑制自发DNA损伤中对其功能重要的区域。