Leucine-rich repeat and WD repeat-containing protein 1

Definition:

Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3 in a cooperative manner with DNA methylation. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability.

References:

[1]. Zhen Shen, et al. A WD-repeat protein stabilizes ORC binding to chromatin. Mol Cell. 2010 Oct 8;40(1):99-111. [Content Brief]

[2]. Till Bartke, et al. Nucleosome-interacting proteins regulated by DNA and histone methylation. Cell. 2010 Oct 29;143(3):470-84. [Content Brief]

[3]. Zhen Shen, et al. Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation. Mol Cell Biol. 2012 Aug;32(15):3107-20. [Content Brief]

[4]. Michiel Vermeulen, et al. Quantitative interaction proteomics and genome-wide profiling of epigenetic histone marks and their readers. Cell. 2010 Sep 17;142(6):967-80. [Content Brief]

[5]. Kui Ming Chan, et al. Leucine-rich repeat and WD repeat-containing protein 1 is recruited to pericentric heterochromatin by trimethylated lysine 9 of histone H3 and maintains heterochromatin silencing. J Biol Chem. 2012 Apr 27;287(18):15024-33. [Content Brief]

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