Microhomology-mediated end-joining chronicles: Tracing the evolutionary footprints of genome protection Review
| Authors: | Sfeir, A.; Tijsterman, M.; McVey, M. |
| Review Title: | Microhomology-mediated end-joining chronicles: Tracing the evolutionary footprints of genome protection |
| Abstract: | The fidelity of genetic information is essential for cellular function and viability. DNA double-strand breaks (DSBs) pose a significant threat to genome integrity, necessitating efficient repair mechanisms. While the predominant repair strategies are usually accurate, paradoxically, error-prone pathways also exist. This review explores recent advances and our understanding of microhomology-mediated end joining (MMEJ), an intrinsically mutagenic DSB repair pathway conserved across organisms. Central to MMEJ is the activity of DNA polymerase theta (Polθ), a specialized polymerase that fuels MMEJ mutagenicity. We examine the molecular intricacies underlying MMEJ activity and discuss its function during mitosis, where the activity of Polθ emerges as a last-ditch effort to resolve persistent DSBs, especially when homologous recombination is compromised. We explore the promising therapeutic applications of targeting Polθ in cancer treatment and genome editing. Lastly, we discuss the evolutionary consequences of MMEJ, highlighting its delicate balance between protecting genome integrity and driving genomic diversity. Copyright © 2024 by the author(s). |
| Keywords: | genetics; review; nonhuman; mitosis; animal; metabolism; animals; homologous recombination; cell function; genetic variability; genetic variation; evolution, molecular; molecular evolution; dna breaks, double-stranded; double stranded dna break; genome; therapy; mutagenesis; dna-directed dna polymerase; dna directed dna polymerase; dna polymerase theta; mutagenicity; replication stress; double strand break repair; dna end-joining repair; dna end joining repair; genetic diversity; humans; human; gene editing; dna directed dna polymerase theta; mitotic repair; mmej; polθ; microhomology mediated end joining repair |
| Journal Title: | Annual Review of Cell and Developmental Biology |
| Volume: | 40 |
| ISSN: | 1081-0706 |
| Publisher: | Annual Reviews |
| Date Published: | 2024-01-01 |
| Start Page: | 195 |
| End Page: | 218 |
| Language: | English |
| DOI: | 10.1146/annurev-cellbio-111822-014426 |
| PUBMED: | 38857538 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Source: Scopus |
