Global synthetic-lethality analysis and yeast functional profiling.

Trends Genet

High Throughput Biology Center, Institute of Genetic Medicine, Department of Biostatistics, Johns Hopkins University School of Medicine, 339 Broadway Research Building, 733 North Broadway, Baltimore, MD 21205, USA.

Published: January 2006

The Saccharomyces genome-deletion project created >5900 'molecularly barcoded' yeast knockout mutants (YKO mutants). The YKO mutant collections have facilitated large-scale analyses of a multitude of mutant phenotypes. For example, both synthetic genetic array (SGA) and synthetic-lethality analysis by microarray (SLAM) methods have been used for synthetic-lethality screens. Global analysis of synthetic lethality promises to identify cellular pathways that 'buffer' each other biologically. The combination of global synthetic-lethality analysis, together with global protein-protein interaction analyses, mRNA expression profiling and functional profiling will, in principle, enable construction of a cellular 'wiring diagram' that will help frame a deeper understanding of human biology and disease.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tig.2005.11.003DOI Listing

Publication Analysis

Top Keywords

synthetic-lethality analysis
12
global synthetic-lethality
8
functional profiling
8
mutants yko
8
global
4
analysis
4
analysis yeast
4
yeast functional
4
profiling saccharomyces
4
saccharomyces genome-deletion
4

Similar Publications

Inactivation of TACC2 epigenetically represses CDKN1A and confers sensitivity to CDK inhibitors.

Med

January 2025

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address:

Background: The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.

Methods: Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.

View Article and Find Full Text PDF

CRISPR/Cas9 Technology Providing the Therapeutic Landscape of Metastatic Prostate Cancer.

Pharmaceuticals (Basel)

November 2024

Department of Biochemistry, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related death in men. Although current therapies can effectively manage the primary tumor, most patients with late-stage disease manifest with metastasis in different organs. From surgery to treatment intensification (TI), several combinations of therapies are administered to improve the prognosis of patients with metastatic PCa.

View Article and Find Full Text PDF

Essential genes, estimated at approximately 20% of the genome, are broadly expressed and required for reproductive success. They are difficult to study, as interfering with their function leads to premature death. Transcription is one of the essential functions of life, and the multi-protein Mediator complex coordinates the regulation of gene expression at nearly every eukaryotic promoter.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers successfully created an infectious clone of HSV-1 by assembling its genome from 11 cloned fragments in yeast using a method called transformation associated recombination.* -
  • They engineered mutations in five specific genes, which are important for the virus's structure and functionality, and discovered that certain combinations of these mutations led to "synthetic lethality," preventing the virus from replicating in specific cell lines.* -
  • The study focused on the mutations of the UL16 and UL21 genes, revealing that viruses lacking both proteins showed immature capsid structures unable to mature into infectious particles, highlighting their potential roles in virus assembly.*
View Article and Find Full Text PDF

AI-assisted generation and in-depth in-silico evaluation of potential inhibitor targeting aurora kinase A (AURKA): An anticancer discovery exploiting synthetic lethality approach.

Arch Biochem Biophys

December 2024

Department of Biotechnology Engineering, Institute of Engineering and Technology, Bundelkhand University, Jhansi, U.P., 284128, India. Electronic address:

Genetic alterations are lead causative agents behind the complex pathologies of cancers which render all treatments unarmed. Such alterations in oncogenes can be treated by direct inhibition by specific drugs while alteration in tumor suppressor genes mediating loss of function is challenging to treat. Identification of synthetic lethal partners to specific tumor suppressor genes and mediating their inhibition can be a potential approach to deal with loss of function mutations.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!