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The Balancing Act of Ribonucleotides in DNA

Overview
Specialty Biochemistry
Date 2016 Mar 22
PMID 26996833
Citations 41
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Abstract

The abundance of ribonucleotides in DNA remained undetected until recently because they are efficiently removed by the ribonucleotide excision repair (RER) pathway, a process similar to Okazaki fragment (OF) processing after incision by Ribonuclease H2 (RNase H2). All DNA polymerases incorporate ribonucleotides during DNA synthesis. How many, when, and why they are incorporated has been the focus of intense work during recent years by many labs. In this review, we discuss recent advances in ribonucleotide incorporation by eukaryotic DNA polymerases that suggest an evolutionarily conserved role for ribonucleotides in DNA. We also review the data that indicate that removal of ribonucleotides has an important role in maintaining genome stability.

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References
1.
Sparks J, Chon H, Cerritelli S, Kunkel T, Johansson E, Crouch R . RNase H2-initiated ribonucleotide excision repair. Mol Cell. 2012; 47(6):980-6. PMC: 3470915. DOI: 10.1016/j.molcel.2012.06.035. View

2.
Reijns M, Bubeck D, Gibson L, Graham S, Baillie G, Jones E . The structure of the human RNase H2 complex defines key interaction interfaces relevant to enzyme function and human disease. J Biol Chem. 2010; 286(12):10530-9. PMC: 3060506. DOI: 10.1074/jbc.M110.177394. View

3.
Pavlov Y, Shcherbakova P, Kunkel T . In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta. Genetics. 2001; 159(1):47-64. PMC: 1461793. DOI: 10.1093/genetics/159.1.47. View

4.
Cavanaugh N, Beard W, Batra V, Perera L, Pedersen L, Wilson S . Molecular insights into DNA polymerase deterrents for ribonucleotide insertion. J Biol Chem. 2011; 286(36):31650-60. PMC: 3173102. DOI: 10.1074/jbc.M111.253401. View

5.
Rydberg B, Game J . Excision of misincorporated ribonucleotides in DNA by RNase H (type 2) and FEN-1 in cell-free extracts. Proc Natl Acad Sci U S A. 2002; 99(26):16654-9. PMC: 139199. DOI: 10.1073/pnas.262591699. View