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The Eyes Absent family: At the intersection of DNA repair, mitosis, and replication
Christopher B Nelson1, Jadon K Wells1, Hilda A Pickett1
1Children's Medical Research Institute, Faculty of Medicine and Health, University of Sydney, Westmead, NSW, Australia.
Abstract:
The Eyes Absent family (EYA1-4) are a group of dual function proteins that act as both tyrosine phosphatases and transcriptional co-activators. EYA proteins play a vital role in development, but are also aberrantly overexpressed in cancers, where they often confer an oncogenic effect. Precisely how the EYAs impact cell biology is of growing interest, fuelled by the therapeutic potential of an expanding repertoire of EYA inhibitors. Recent functional studies suggest that the EYAs are important players in the regulation of genome maintenance pathways including DNA repair, mitosis, and DNA replication. While the characterized molecular mechanisms have predominantly been ascribed to EYA phosphatase activities, EYA co-transcriptional activity has also been found to impact the expression of genes that support these pathways. This indicates functional convergence of EYA phosphatase and co-transcriptional activities, highlighting the emerging importance of the EYA protein family at the intersection of genome maintenance mechanisms. In this review, we discuss recent progress in defining EYA protein substrates and transcriptional effects, specifically in the context of genome maintenance. We then outline future directions relevant to the field and discuss the clinical utility of EYA inhibitors.
Insights
The Eyes Absent (EYA) protein family, involved in development and cancer, regulates genome maintenance through dual phosphatase and co-activator functions. Understanding EYA
Area of Science:
- Molecular Biology
- Cancer Biology
- Genetics
Background:
- The Eyes Absent (EYA) protein family (EYA1-4) comprises dual-function proteins with tyrosine phosphatase and transcriptional co-activator activities.
- EYA proteins are crucial for development but are frequently overexpressed in various cancers, contributing to oncogenesis.
- Growing interest surrounds EYA proteins due to their emerging roles in genome maintenance and the development of targeted inhibitors.
Purpose of the Study:
- To review recent advancements in understanding EYA protein functions within genome maintenance pathways.
- To explore the convergence of EYA's phosphatase and co-transcriptional activities in regulating DNA repair, mitosis, and replication.
- To discuss the clinical implications and therapeutic potential of EYA inhibitors.
Main Methods:
- Review of recent functional studies and molecular mechanisms.
- Analysis of EYA protein substrates and transcriptional targets.
- Discussion of emerging research in genome maintenance pathways.
Main Results:
- EYA proteins significantly regulate key genome maintenance processes, including DNA repair, mitosis, and DNA replication.
- Both EYA phosphatase activity and co-transcriptional activity contribute to the regulation of genes involved in these pathways.
- Functional convergence between EYA's dual activities highlights its central role at the intersection of genome maintenance.
Conclusions:
- The EYA protein family is critically involved in maintaining genome stability through integrated phosphatase and co-transcriptional functions.
- Further research into EYA substrates and transcriptional targets will elucidate their precise roles in genome maintenance.
- EYA inhibitors represent a promising therapeutic strategy for cancers associated with EYA overexpression.
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