| RRC ID |
46674
|
| 著者 |
Skjeldam HK, Kassahun H, Fensgård O, SenGupta T, Babaie E, Lindvall JM, Arczewska K, Nilsen H.
|
| タイトル |
Loss of Caenorhabditis elegans UNG-1 uracil-DNA glycosylase affects apoptosis in response to DNA damaging agents.
|
| ジャーナル |
DNA Repair (Amst)
|
| Abstract |
The nematode Caenorhabditis elegans has been used extensively to study responses to DNA damage. In contrast, little is known about DNA repair in this organism. C. elegans is unusual in that it encodes few DNA glycosylases and the uracil-DNA glycosylase (UDG) encoded by the ung-1 gene is the only known UDG. C. elegans could therefore become a valuable model organism for studies of the genetic interaction networks involving base excision repair (BER). As a first step towards characterization of BER in C. elegans, we show that the UNG-1 protein is an active uracil-DNA glycosylase. We demonstrate that an ung-1 mutant has reduced ability to repair uracil-containing DNA but that an alternative Ugi-inhibited activity is present in ung-1 nuclear extracts. Finally, we demonstrate that ung-1 mutants show altered levels of apoptotic cell corpses formed in response to DNA damaging agents. Increased apoptosis in the ung-1 mutant in response to ionizing radiation (IR) suggests that UNG-1 contributes to repair of IR-induced DNA base damage in vivo. Following treatment with paraquat however, the apoptotic corpse-formation was reduced. Gene expression profiling suggests that this phenotype is a consequence of compensatory transcriptomic shifts that modulate oxidative stress responses in the mutant and not an effect of reduced DNA damage signaling.
|
| 巻・号 |
9(8)
|
| ページ |
861-70
|
| 公開日 |
2010-8-5
|
| DOI |
10.1016/j.dnarep.2010.04.009
|
| PII |
S1568-7864(10)00145-X
|
| PMID |
20493785
|
| MeSH |
Animals
Apoptosis / radiation effects
Caenorhabditis elegans / enzymology*
Caenorhabditis elegans / genetics
Caenorhabditis elegans / radiation effects
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism*
DNA Damage / radiation effects
DNA Repair / physiology*
Gene Expression Profiling / methods
Mutation*
Paraquat / pharmacology*
Uracil-DNA Glycosidase / genetics
Uracil-DNA Glycosidase / metabolism*
|
| IF |
3.339
|
| 引用数 |
9
|
|
WOS 分野
|
TOXICOLOGY
GENETICS & HEREDITY
|
| リソース情報 |
| 線虫 |
tm2862 |
