期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 209, 期 8, 页码 1419-1426出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20120876
关键词
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资金
- German Research Foundation [Klinische Forschergruppe KFO 249, Ro2133/6-1]
- Medical Faculty Carl Gustav Carus, TU-Dresden [60.230, 60.294]
Ribonucleases H (RNases H) are endonucleases which cleave the RNA moiety of RNA/DNA hybrids. Their function in mammalian cells is incompletely understood. RNase H2 mutations cause Aicardi-GoutiSres syndrome, an inflammatory condition clinically overlapping with lupus erythematosus. We show that RNase H2 is essential in mouse embryonic development. RNase H2-deficient cells proliferated slower than control cells and accumulated in G2/M phase due to chronic activation of a DNA damage response associated with an increased frequency of single-strand breaks, increased histone H2AX phosphorylation, and induction of p53 target genes, most prominently the cyclin-dependent kinase inhibitor 1 encoding cell cycle inhibitor p21. RNase H2-deficient cells featured an increased genomic ribonucleotide load, suggesting that unrepaired ribonucleotides trigger the DNA damage response in these cells. Collectively, we show that RNase H2 is essential to remove ribonucleotides from the mammalian genome to prevent DNA damage.
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