Emerging roles of MCPH1: expedition from primary microcephaly to cancer
Thejaswini Venkatesh1, Padmanaban S Suresh2
1Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India.
Abstract:
Genetic mutations in microcephalin1 (MCPH1) cause primary autosomal recessive microcephaly which is characterized by a marked reduction in brain size. MCPH1 encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also, it is a key regulator of DNA repair pathway and cell cycle checkpoints. Interestingly, in the past few years, many research studies have explored the role of MCPH1, a neurodevelopmental gene in several cancers and its tumor suppressor functions have been elucidated. Given the diverse new emerging roles, it becomes critical to review and summarize the multiple roles of MCPH1 that is currently lacking in the literature. In this review after systematic analysis of literature, we summarise the multiple functional roles of MCPH1 in centrosomal, DNA repair and apoptotic pathways. Additionally, we discuss the considerable efforts taken to understand the implications of MCPH1 in diseases such as primary microcephaly and its other emerging association with cancer and otitis media. The promising view is that MCPH1 has distinct roles and its clinical associations in various diseases makes it an attractive therapeutic target.
Insights
Genetic mutations in microcephalin1 (MCPH1) cause primary microcephaly. This review summarizes MCPH1
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Microcephalin1 (MCPH1) mutations lead to primary autosomal recessive microcephaly, a condition of reduced brain size.
- MCPH1 encodes a centrosomal protein regulating DNA repair and cell cycle checkpoints.
- Emerging research highlights MCPH1's role in cancer, suggesting tumor suppressor functions.
Purpose of the Study:
- To systematically review and summarize the diverse functional roles of MCPH1.
- To consolidate current knowledge on MCPH1's implications in various diseases.
- To highlight MCPH1 as a potential therapeutic target.
Main Methods:
- Systematic literature analysis.
- Review of studies on MCPH1's function in centrosomal, DNA repair, and apoptotic pathways.
- Discussion of MCPH1's association with primary microcephaly, cancer, and otitis media.
Main Results:
- MCPH1 plays critical roles in centrosomal function, DNA repair, and apoptosis.
- MCPH1 is implicated in primary microcephaly and exhibits emerging associations with cancer.
- Evidence suggests tumor suppressor functions for MCPH1.
Conclusions:
- MCPH1 has multifaceted roles beyond its known function in microcephaly.
- MCPH1's diverse functions and clinical associations present it as a promising therapeutic target.
- Further research into MCPH1's pathways could yield novel treatment strategies for associated diseases.
