Summary information and primary citation
- PDB-id
-
4hht;
DSSR-derived features in text and
JSON formats
- Class
- hydrolase-DNA
- Method
- X-ray (3.1 Å)
- Summary
- T. maritima rnase h2 g21s in complex with nucleic acid
substrate and calcium ions
- Reference
-
Chon H, Sparks JL, Rychlik M, Nowotny M, Burgers PM,
Crouch RJ, Cerritelli SM (2013): "RNase H2
roles in genome integrity revealed by unlinking its
activities." Nucleic Acids Res.,
41, 3130-3143. doi: 10.1093/nar/gkt027.
- Abstract
- Ribonuclease H2 (RNase H2) protects genome integrity by
its dual roles of resolving transcription-related R-loops
and ribonucleotides incorporated in DNA during replication.
To unlink these two functions, we generated a Saccharomyces
cerevisiae RNase H2 mutant that can resolve R-loops but
cannot cleave single ribonucleotides in DNA. This mutant
definitively correlates the 2-5 bp deletions observed in
rnh201Δ strains with single rNMPs in DNA. It also
establishes a connection between R-loops and Sgs1-mediated
replication reinitiation at stalled forks and identifies
R-loops uniquely processed by RNase H2. In mouse, deletion
of any of the genes coding for RNase H2 results in
embryonic lethality, and in humans, RNase H2 hypomorphic
mutations cause Aicardi-Goutières syndrome (AGS), a
neuroinflammatory disorder. To determine the contribution
of R-loops and rNMP in DNA to the defects observed in AGS,
we characterized in yeast an AGS-related mutation, which is
impaired in processing both substrates, but has sufficient
R-loop degradation activity to complement the defects of
rnh201Δ sgs1Δ strains. However, this AGS-related mutation
accumulates 2-5 bp deletions at a very similar rate as the
deletion strain.
