Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity.

ABSTRACT: 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-Goutières 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

SUBMITTER: Hiller B 

PROVIDER: S-EPMC3409502 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature