Leucine Rich Repeats And WD Repeat Domain Containing Protein 1 (LRWD1)

A highly conserved, leucine-rich repeats and WD40 repeat domain-containing protein 1 (LRWD1) or ORC-associated (ORCA) in human cells that interacts with ORC and modulates chromatin association of ORC. ORCA colocalizes with ORC and shows similar cell-cycle dynamics. ORCA efficiently recruits ORC to chromatin. Depletion of ORCA in human primary cells and embryonic stem cells results in loss of ORC association to chromatin, concomitant reduction of MCM binding, and a subsequent accumulation in G1 phase. Reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression. The ORC complex, including LRWD1, binds to the three most prominent transcriptional repressive lysine methylation sites.