E3 ubiquitin ligase that plays important roles in DNA methylation, histone modifications, cell cycle and DNA repair ( , ). Acts as a specific reader for 5-hydroxymethylcytosine (5hmC) and thereby recruits various substrates to these sites to ubiquitinate them (, ). This activity also allows the maintenance of 5mC levels at specific genomic loci and regulates neuron-related gene expression (By similarity). Participates in cell cycle regulation by ubiquitinating cyclins CCND1 and CCNE1 and thereby inducing G1 arrest ( ). Ubiquitinates also PCNP leading to its degradation by the proteasome (, ). Plays an active role in DNA damage repair by ubiquitinating p21/CDKN1A leading to its proteasomal degradation . Promotes also DNA repair by acting as an interstrand cross-links (ICLs) sensor. Mechanistically, cooperates with UHRF1 to ensure recruitment of FANCD2 to ICLs, leading to FANCD2 monoubiquitination and subsequent activation . Contributes to UV-induced DNA damage response by physically interacting with ATR in response to irradiation, thereby promoting ATR activation .
Subcellular locations: Nucleus, Chromosome
Enriched at genomic loci that are enriched for 5-hydroxymethylcytosine (5hmC).