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:3.1.26.4 (
RNase H
)
2,751
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SR proteins constitute a family of pre-mRNA splicing factors now thought to play several roles in mRNA metabolism in metazoan cells. Here we provide evidence that a prototypical SR protein,
ASF/SF2
, is unexpectedly required for maintenance of genomic stability. We first show that in vivo depletion of
ASF/SF2
results in a hypermutation phenotype likely due to DNA rearrangements, reflected in the rapid appearance of DNA double-strand breaks and high-molecular-weight DNA fragments. Analysis of DNA from
ASF/SF2
-depleted cells revealed that the nontemplate strand of a transcribed gene was single stranded due to formation of an RNA:DNA hybrid, R loop structure. Stable overexpression of
RNase H
suppressed the DNA-fragmentation and hypermutation phenotypes. Indicative of a direct role,
ASF/SF2
prevented R loop formation in a reconstituted in vitro transcription reaction. Our results support a model by which recruitment of
ASF/SF2
to nascent transcripts by RNA polymerase II prevents formation of mutagenic R loop structures.
...
PMID:Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability. 1609 57
