The emerging role of MCPH1/BRIT1 in carcinogenesis

Abstract

The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.

Functional analysis of a novel intronic variant of MCPH1 with autosomal recessive primary microcephaly

“…It contains 835 amino acids with ∼110 kDa molecular weight and exists in two major subtypes whose were similar in fetal tissue without cell type specificity, but both were subject to antagonistic regulation during the cell cycle [ 9 ]. MCPH1 is composed of three BRCT domains, located at the N- terminal domain (1–93 aa), and at the C- terminal domain (672–730 aa) and (751–833 aa) [ 10 , 11 ]. The BRCT domain is a conserved region which interacts with phosphopeptides and is commonly found in proteins associated with DNA damage response signaling and cell cycle regulation.…”