| RRC ID |
45773
|
| Author |
Koole W, van Schendel R, Karambelas AE, van Heteren JT, Okihara KL, Tijsterman M.
|
| Title |
A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites.
|
| Journal |
Nat Commun
|
| Abstract |
Genomes contain many sequences that are intrinsically difficult to replicate. Tracts of tandem guanines, for instance, have the potential to adopt stable G-quadruplex structures, which are prone to cause genome alterations. Here we describe G4 DNA-induced mutagenesis in Caenorhabditis elegans and identify a non-canonical DNA break repair mechanism that generates deletions characterized by an extremely narrow size distribution, minimal homology of exactly one nucleotide at the junctions, and by the occasional presence of templated insertions. This typical mutation profile is fully dependent on the A-family polymerase Theta, the absence of which leads to profound loss of sequences surrounding G4 motifs. Theta-mediated end-joining prevails over non-homologous end joining and homologous recombination and prevents genomic havoc at replication fork barriers at the expense of small deletions. G4 DNA-induced deletions also manifest in the genomes of wild isolates of C. elegans, indicating a protective role for this pathway during evolution.
|
| Volume |
5
|
| Pages |
3216
|
| Published |
2014-1-1
|
| DOI |
10.1038/ncomms4216
|
| PII |
ncomms4216
|
| PMID |
24496117
|
| MeSH |
Animals
Base Sequence
Caenorhabditis elegans
DNA Breaks, Double-Stranded*
DNA Repair*
DNA-Directed DNA Polymerase / metabolism*
Evolution, Molecular
G-Quadruplexes*
Molecular Sequence Data
|
| IF |
12.121
|
| Times Cited |
97
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| C.elegans |
tm2572
tm2606
tm2026
tm1145 |
