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PDBsum entry 4hht
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Hydrolase/DNA
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PDB id
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4hht
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References listed in PDB file
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Key reference
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Title
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Rnase h2 roles in genome integrity revealed by unlinking its activities.
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Authors
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H.Chon,
J.L.Sparks,
M.Rychlik,
M.Nowotny,
P.M.Burgers,
R.J.Crouch,
S.M.Cerritelli.
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Ref.
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Nucleic Acids Res, 2013,
41,
3130-3143.
[DOI no: ]
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PubMed id
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Abstract
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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.
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