Reference - Detail
| RRC ID | 45650 |
|---|---|
| Author | van Schendel R, Roerink SF, Portegijs V, van den Heuvel S, Tijsterman M. |
| Title | Polymerase Θ is a key driver of genome evolution and of CRISPR/Cas9-mediated mutagenesis. |
| Journal | Nat Commun |
| Abstract |
Cells are protected from toxic DNA double-stranded breaks (DSBs) by a number of DNA repair mechanisms, including some that are intrinsically error prone, thus resulting in mutations. To what extent these mechanisms contribute to evolutionary diversification remains unknown. Here, we demonstrate that the A-family polymerase theta (POLQ) is a major driver of inheritable genomic alterations in Caenorhabditis elegans. Unlike somatic cells, which use non-homologous end joining (NHEJ) to repair DNA transposon-induced DSBs, germ cells use polymerase theta-mediated end joining, a conceptually simple repair mechanism requiring only one nucleotide as a template for repair. Also CRISPR/Cas9-induced genomic changes are exclusively generated through polymerase theta-mediated end joining, refuting a previously assumed requirement for NHEJ in their formation. Finally, through whole-genome sequencing of propagated populations, we show that only POLQ-proficient animals accumulate genomic scars that are abundantly present in genomes of wild C. elegans, pointing towards POLQ as a major driver of genome diversification. |
| Volume | 6 |
| Pages | 7394 |
| Published | 2015-6-16 |
| DOI | 10.1038/ncomms8394 |
| PII | ncomms8394 |
| PMID | 26077599 |
| PMC | PMC4490562 |
| MeSH | Animals CRISPR-Cas Systems* Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics* DNA Breaks, Double-Stranded DNA End-Joining Repair* DNA Polymerase theta DNA Repair DNA-Directed DNA Polymerase / metabolism* Evolution, Molecular Genome, Helminth / genetics* Germ Cells / metabolism* Germ-Line Mutation / genetics* Mutagenesis* Mutation |
| IF | 12.121 |
| Times Cited | 41 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 13 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2073 tm1145 tm1842 tm2026 |