| RRC ID |
12677
|
| 著者 |
Bailly AP, Freeman A, Hall J, Déclais AC, Alpi A, Lilley DM, Ahmed S, Gartner A.
|
| タイトル |
The Caenorhabditis elegans homolog of Gen1/Yen1 resolvases links DNA damage signaling to DNA double-strand break repair.
|
| ジャーナル |
PLoS Genet
|
| Abstract |
DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR), which can involve Holliday junction (HJ) intermediates that are ultimately resolved by nucleolytic enzymes. An N-terminal fragment of human GEN1 has recently been shown to act as a Holliday junction resolvase, but little is known about the role of GEN-1 in vivo. Holliday junction resolution signifies the completion of DNA repair, a step that may be coupled to signaling proteins that regulate cell cycle progression in response to DNA damage. Using forward genetic approaches, we identified a Caenorhabditis elegans dual function DNA double-strand break repair and DNA damage signaling protein orthologous to the human GEN1 Holliday junction resolving enzyme. GEN-1 has biochemical activities related to the human enzyme and facilitates repair of DNA double-strand breaks, but is not essential for DNA double-strand break repair during meiotic recombination. Mutational analysis reveals that the DNA damage-signaling function of GEN-1 is separable from its role in DNA repair. GEN-1 promotes germ cell cycle arrest and apoptosis via a pathway that acts in parallel to the canonical DNA damage response pathway mediated by RPA loading, CHK1 activation, and CEP-1/p53-mediated apoptosis induction. Furthermore, GEN-1 acts redundantly with the 9-1-1 complex to ensure genome stability. Our study suggests that GEN-1 might act as a dual function Holliday junction resolvase that may coordinate DNA damage signaling with a late step in DNA double-strand break repair.
|
| 巻・号 |
6(7)
|
| ページ |
e1001025
|
| 公開日 |
2010-7-15
|
| DOI |
10.1371/journal.pgen.1001025
|
| PMID |
20661466
|
| PMC |
PMC2908289
|
| MeSH |
Animals
Apoptosis
Caenorhabditis elegans / genetics*
Cell Cycle
DNA Breaks, Double-Stranded*
DNA Damage*
DNA Repair*
Genomic Instability
Germ Cells
Holliday Junction Resolvases / genetics
Holliday Junction Resolvases / physiology*
Meiosis
Signal Transduction / genetics
|
| IF |
5.175
|
| 引用数 |
63
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| 線虫 |
tm2940
tm1579
tm853
tm1670
tm899 |
