Recruitment of Dnmt1 roles of the SRA protein Np95 (Uhrf1) and other factors

Abstract

Dnmt1, the major DNA methyltransferase enzyme in mammals, mediates inheritance of DNA methylation from parent cell to daughter cells. However, the mechanism by which Dnmt1 is recruited into the replication fork (RF) during cell division was not fully understood. Recently, the mammalian SRA (Set and RING-finger-associated domain) protein Np95 (nuclear protein 95kDa) (also known as Uhrf1) was found to help recruit Dnmt1 to hemimethylated CpGs generated at the RF during the S-phase. Here, we will discuss in detail how Np95 recognizes hemimethylated DNA through its SRA domain and recruits Dnmt1 to these sites. In addition, we will examine the functions of other recruiter/interactor molecules that are involved in Dnmt1 localization both locus specifically and globally. Elucidation of the pathways by which Dnmt1 is recruited and identification of the molecules that are involved in this process will provide key information about the mechanisms of genome reprogramming and the epigenetic differences between normal and transformed cells.