Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.22.1 (
DNase II
)
429
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
DNase II
digests DNA in endolysosomes. In the absence of
DNase II
, undigested DNA activates cytoplasmic DNA-sensing pathways. Little is known, however, about the role of
DNase II
in endolysosomal DNA sensing by TLR9. Here we show that
DNase II
is required for TLR9. We test two types of TLR9 ligands, CpG-A and CpG-B, and show that only CpG-A response is impaired in
DNase II
-deficient dendritic cells (DCs). Enzymatically inactive
DNase II
mutants cannot rescue CpG-A responses.
DNase II
cleaves CpG-A from 20-mer to 11-12-mer. The 3'11-mer CpG-A fragment activates
DNase II
-deficient DCs. CpG-A shows higher co-localization with
LAMP-2
(+) lysosomes than CpG-B and induces
DNase II
localization in
LAMP-2
(+) lysosomes. Moreover, we demonstrate that
DNase II
is required for TLR9 activation by bacterial genomic DNA. Taken together, these results demonstrate that TLR9 responds to DNA fragments generated by
DNase II
.
...
PMID:DNase II-dependent DNA digestion is required for DNA sensing by TLR9. 2560 Mar 58