Analysis of Ribonucleotide Removal from DNA by Human Nucleotide Excision Repair.
Ribonucleotides are incorporated into the genome during DNA replication. The enzyme RNase H2 plays a critical role in targeting the removal of these ribonucleotides from DNA, and defects in RNase H2 activity are associated with both genomic instability and the human autoimmune/inflammatory disorder Aicardi-Goutières syndrome. Whether additional general DNA repair mechanisms contribute to ribonucleotide removal from DNA in human cells is not known. Because of its ability to act on a wide variety of substrates, we examined a potential role for canonical nucleotide excision repair in the removal of ribonucleotides from DNA. However, using highly sensitive dual incision/excision assays, we find that ribonucleotides are not efficiently targeted by the human nucleotide excision repair system in vitro or in cultured human cells. These results suggest that nucleotide excision repair is unlikely to play a major role in the cellular response to ribonucleotide incorporation in genomic DNA in human cells.
From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
Laura A
LA
Lindsey-Boltz
From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
Michael G
MG
Kemp
From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
Jinchuan
J
Hu
From the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 aziz_sancar@med.unc.edu.
Aziz
A
Sancar
D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D012265:Ribonucleotides / Q000378:metabolism*
D012265:Ribonucleotides; D004247:DNA
DNA damage; DNA damage response; DNA repair; DNA replication; autoimmune disease; autoimmunity; genomic instability; inflammation; innate immunity; mutagenesis; nucleotide excision repair; ribonucleotides