Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1)

Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1) is a chromatin-associated protein with a leucine-rich repeat (LRR) domain and several WD40 repeats. LRWD1 functions primarily as a scaffold facilitating the recruitment and stabilization of the origin recognition complex (ORC) to chromatin during the G1 phase, which is critical for initiating DNA replication and ensuring proper cell cycle progression. LRWD1 also binds repressive histone marks (such as H3K9me3, H3K27me3, and H4K20me3) and methylated DNA, contributing to heterochromatin maintenance and gene silencing. In testicular tissue, LRWD1 expression is essential for normal spermatogenesis and sperm motility, partly due to its epigenetic regulation by promoter methylation. Aberrant LRWD1 activity or expression has been implicated in male infertility and is associated with certain cancers. Modulation of LRWD1 expression by epigenetic drugs (e.g., DNA methylation inhibitors) has been explored primarily in cellular models[1][2][3].

Other names

ORCACENP-33Origin recognition complex-associated proteinORC-associated proteinCentromere protein 33DKFZp434K1815testicular tissue protein Li 4

Modulation of DNA methylation status influences LRWD1 transcription and protein expression[1]. Drugs altering methylation (5-Aza-2′-deoxycytidine, floxuridine) do so indirectly via epigenetic regulation rather than direct binding[1].