MutY-glycosylase: an overview on mutagenesis and activities beyond the GO system.

MutY is a glycosylase known for its role in DNA base excision repair (BER). It is critically important in the prevention of DNA mutations derived from 7,8-dihydro-8-oxoguanine (8-oxoG), which are the major lesions resulting from guanine oxidation. MutY has been described as a DNA repair enzyme in the GO system responsible for removing adenine residues misincorporated in 8-oxoG:A mispairs, avoiding G:C to T:A mutations. Further studies have shown that this enzyme binds to other mispairs, interacts with several enzymes, avoids different transversions/transitions in DNA, and is involved in different repair pathways. Additional activities have been reported for MutY, such as the repair of replication errors in newly synthesized DNA strands through its glycosylase activity. Moreover, MutY is a highly conserved enzyme present in several prokaryotic and eukaryotic organisms. MutY defects are associated with a hereditary colorectal cancer syndrome termed MUTYH-associated polyposis (MAP). Here, we have reviewed the roles of MutY in the repair of mispaired bases in DNA as well as its activities beyond the GO system.

The RNA-Binding Protein Musashi1: A Major Player in Intestinal Epithelium Renewal and Colon Cancer Development.

Aberrant gene expression is the cause and the consequence of tumorigenesis. A major component of gene expression is translation regulation; a process whose main players are RNA-binding-proteins (RBPs). More than 800 RBPs have been identified in the human genome and several of them have been shown to control gene networks associated with relevant cancer processes. A more systematic characterization of RBPs starts to reveal that similar to transcription factors, they can function as tumor suppressors or oncogenes. A relevant example is Musashi1 (Msi1), which is emerging as a critical regulator of tumorigenesis in multiple cancer types, including colon cancer. Msi1 is a stem marker in several tissues and is critical in maintaining the balance between self-renewal and differentiation. However, a boost in Msi1 expression can most likely lead cells towards an oncogenic pathway. In this article, we discuss the parallels between Msi1 function in normal renewal of intestinal epithelium and in colon cancer.