ArticleNucleic acids research2003
Lack of sugar discrimination by human Pol mu requires a single glycine residue.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- Ribonucleotide errors, RNase HII, and ribonucleotide excision repair.Critical reviews in biochemistry and molecular biology · 2026Review
- DNA polymerase λ Loop1 variant yields unexpected gain-of-function capabilities in nonhomologous end-joining.DNA repair · 2024Article
- Substrate Specificity Diversity of Human Terminal Deoxynucleotidyltransferase May Be a Naturally Programmed Feature Facilitating Its Biological Function.International journal of molecular sciences · 2024Article
- For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.International journal of molecular sciences · 2023Review
- Ribonucleotide Incorporation by Eukaryotic B-Family Replicases and Its Implications for Genome Stability.Annual review of biochemistry · 2022Review
- Review
- Structural basis for proficient oxidized ribonucleotide insertion in double strand break repair.Nature communications · 2021Article
- Mechanism of genome instability mediated by human DNA polymerase mu misincorporation.Nature communications · 2021Article
- Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.Nature communications · 2021Article
- Ribonucleotide incorporation into DNA during DNA replication and its consequences.Critical reviews in biochemistry and molecular biology · 2021Review
- The molecular basis and disease relevance of non-homologous DNA end joining.Nature reviews. Molecular cell biology · 2020Review
- DNA polymerase mu: An inflexible scaffold for substrate flexibility.DNA repair · 2020Review
- Polymerase μ in non-homologous DNA end joining: importance of the order of arrival at a double-strand break in a purified system.Nucleic acids research · 2020Article
- One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.International journal of molecular sciences · 2020Review
- Structural Determinants Responsible for the Preferential Insertion of Ribonucleotides by Bacterial NHEJ PolDom.Biomolecules · 2020Article
- Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2'-guanosine.Nucleic acids research · 2019Article
- Ribonucleotide discrimination by translesion synthesis DNA polymerases.Critical reviews in biochemistry and molecular biology · 2018Review
- Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism.Annual review of biochemistry · 2018Review
- Human DNA polymerase η accommodates RNA for strand extension.The Journal of biological chemistry · 2017Article
- Polμ tumor variants decrease the efficiency and accuracy of NHEJ.Nucleic acids research · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA polymerase mu (Pol mu) is a novel family X DNA polymerase that has been suggested to play a role in micro-homology mediated joining and repair of double strand breaks. We show here that human Pol mu is not able to discriminate against the 2'-OH group of the sugar moiety. It inserts rNTPs with an efficiency that is <10-fold lower than that of dNTPs, in sharp contrast with the >1000-fold discrimination characteristic of most DNA-dependent DNA polymerases. The lack of sugar discrimination by Pol mu is demonstrated by its ability to add rNTPs to both DNA and RNA primer strands, and to insert both deoxy- and ribonucleotides on growing nucleic acid chains. 3D-modelling of human Pol mu based on the available Pol beta and TdT structural information allowed us to predict candidate residues involved in sugar discrimination. Thus, a single amino acid substitution in which Gly433 residue of Pol mu was mutated to the consensus tyrosine present in Pol beta, produced a strong increase in the discrimination against ribonucleotides. The unusual capacity to insert both rNTPs and dNTPs will be discussed in the context of the predicted roles of Pol mu in DNA repair.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.