The Yeast High Mobility Group Protein HMO1 Facilitates DNA End‐Joining and Functions in DNA Double Strand Break Repair

Abstract

The Saccharomyces cerevisiae high mobility group protein HMO1 has two DNA binding domains, box A and box B, and a lysine‐rich C‐terminal tail. Among other functions, HMO1 has been implicated in mutagenesis control. Our in vitro assay shows that HMO1 promotes DNA end‐joining in presence of T4 DNA ligase. Analysis of truncated HMO1 variants shows that enhanced DNA end‐joining is critically dependent on the C‐terminal domain, but that the box A domain is dispensable. Since interactions between box A and the C‐terminal domain are thought to be required for DNA bending, DNA end‐joining may involve a binding mode that does not depend on significant changes in DNA topology. Notably, transformation of an hmo1δ strain and its isogenic HMO1 parent strain with linearized plasmid DNA shows significantly reduced transformation efficiency for the hmo1δ strain, consistent with a role for HMO1 in DNA double strand break repair by non‐homologous end‐joining. While these data are consistent with an accessory role of HMO1 in apposition of DNA ends in preparation for association with the non‐homologous end‐joining apparatus, the reported physical interaction between HMO1 and components of various chromatin remodeling complexes suggests that an indirect role in chromatin remodeling at double strand break sites is also possible.