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Conserved overlapping gene arrangement, restricted expression, and biochemical activities of DNA polymerase ν (POLN).

Takata K, Tomida J, Reh S, Swanhart LM, Takata M, Hukriede NA, Wood RD - J. Biol. Chem. (2015)

Bottom Line: Consistent with this, injection of POLN-specific morpholino antisense oligonucleotides did not interfere with zebrafish embryonic development.These properties are conserved with the human enzyme.Although the physiological function of pol ν remains to be clarified, this study uncovers distinctive aspects of its expression control and evolutionarily conserved properties of this DNA polymerase.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, the University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, ktakata@mdanderson.org.

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Conserved features of DNA polymerase ν (POLN).A, domains of human POLN, POLQ, and HELQ. Defined motifs are shown by vertical black stripes. B, sequence alignment of POLN-N, exoIII, motif 3, and motif 4 of POLN from three fish (zebrafish, maylandia, and tilapia), two birds (falcon and sparrow), four mammals (mouse, elephant, monkey, and human), and prokaryotic A-family DNA polymerases, E. coli DNA polymerase I (EcpolI) and Rhodococcus erythropolis DNA polymerase I (Rhodococcus). Residues are colored in similarity groups as follows: {K, R, H}, {D, E}, {I, L, V, M}, {F, Y, W}, {Q, N}, {G, A}, {S, T}, {P}, and {C}. Perfectly conserved residues are denoted by *, and highly or relatively conserved residues are denoted by colons and periods, respectively. The open arrowheads show the residues Asp-902 and Arg-957 of zebrafish POLN substituted in this study. The closed arrowhead shows an Asp residue essential for 3′–5′-exonuclease (exo) activity, which is absent in POLN. The sequence alignment was carried out using the Clustal X program.
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Figure 1: Conserved features of DNA polymerase ν (POLN).A, domains of human POLN, POLQ, and HELQ. Defined motifs are shown by vertical black stripes. B, sequence alignment of POLN-N, exoIII, motif 3, and motif 4 of POLN from three fish (zebrafish, maylandia, and tilapia), two birds (falcon and sparrow), four mammals (mouse, elephant, monkey, and human), and prokaryotic A-family DNA polymerases, E. coli DNA polymerase I (EcpolI) and Rhodococcus erythropolis DNA polymerase I (Rhodococcus). Residues are colored in similarity groups as follows: {K, R, H}, {D, E}, {I, L, V, M}, {F, Y, W}, {Q, N}, {G, A}, {S, T}, {P}, and {C}. Perfectly conserved residues are denoted by *, and highly or relatively conserved residues are denoted by colons and periods, respectively. The open arrowheads show the residues Asp-902 and Arg-957 of zebrafish POLN substituted in this study. The closed arrowhead shows an Asp residue essential for 3′–5′-exonuclease (exo) activity, which is absent in POLN. The sequence alignment was carried out using the Clustal X program.

Mentions: Human DNA polymerase ν is encoded by the POLN gene. It is a member of the DNA polymerase A-family (2–4). The DNA polymerase domain of POLN is related to that of mammalian POLQ/Drosophila Mus308 (Fig. 1A) (2, 5). Mus308 and POLQ participate in a pathway of DNA double strand break repair by alternative end joining (6, 7). Defects in Mus308 or POLQ confer hypersensitivity to various DNA-damaging agents (7–9). Both mus308 and POLQ also encode an N-terminal helicase-like domain (10, 11). A third member of this gene family, HELQ, encodes a helicase domain similar to that of POLQ/Mus308 (Fig. 1A) (12). HELQ interacts with ataxia telangiectasia and Rad3-related (ATR) and with homologous recombination-related RAD51 paralogs and participates in DNA cross-link resistance in human cells (13–15).


Conserved overlapping gene arrangement, restricted expression, and biochemical activities of DNA polymerase ν (POLN).

Takata K, Tomida J, Reh S, Swanhart LM, Takata M, Hukriede NA, Wood RD - J. Biol. Chem. (2015)

Conserved features of DNA polymerase ν (POLN).A, domains of human POLN, POLQ, and HELQ. Defined motifs are shown by vertical black stripes. B, sequence alignment of POLN-N, exoIII, motif 3, and motif 4 of POLN from three fish (zebrafish, maylandia, and tilapia), two birds (falcon and sparrow), four mammals (mouse, elephant, monkey, and human), and prokaryotic A-family DNA polymerases, E. coli DNA polymerase I (EcpolI) and Rhodococcus erythropolis DNA polymerase I (Rhodococcus). Residues are colored in similarity groups as follows: {K, R, H}, {D, E}, {I, L, V, M}, {F, Y, W}, {Q, N}, {G, A}, {S, T}, {P}, and {C}. Perfectly conserved residues are denoted by *, and highly or relatively conserved residues are denoted by colons and periods, respectively. The open arrowheads show the residues Asp-902 and Arg-957 of zebrafish POLN substituted in this study. The closed arrowhead shows an Asp residue essential for 3′–5′-exonuclease (exo) activity, which is absent in POLN. The sequence alignment was carried out using the Clustal X program.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591814&req=5

Figure 1: Conserved features of DNA polymerase ν (POLN).A, domains of human POLN, POLQ, and HELQ. Defined motifs are shown by vertical black stripes. B, sequence alignment of POLN-N, exoIII, motif 3, and motif 4 of POLN from three fish (zebrafish, maylandia, and tilapia), two birds (falcon and sparrow), four mammals (mouse, elephant, monkey, and human), and prokaryotic A-family DNA polymerases, E. coli DNA polymerase I (EcpolI) and Rhodococcus erythropolis DNA polymerase I (Rhodococcus). Residues are colored in similarity groups as follows: {K, R, H}, {D, E}, {I, L, V, M}, {F, Y, W}, {Q, N}, {G, A}, {S, T}, {P}, and {C}. Perfectly conserved residues are denoted by *, and highly or relatively conserved residues are denoted by colons and periods, respectively. The open arrowheads show the residues Asp-902 and Arg-957 of zebrafish POLN substituted in this study. The closed arrowhead shows an Asp residue essential for 3′–5′-exonuclease (exo) activity, which is absent in POLN. The sequence alignment was carried out using the Clustal X program.
Mentions: Human DNA polymerase ν is encoded by the POLN gene. It is a member of the DNA polymerase A-family (2–4). The DNA polymerase domain of POLN is related to that of mammalian POLQ/Drosophila Mus308 (Fig. 1A) (2, 5). Mus308 and POLQ participate in a pathway of DNA double strand break repair by alternative end joining (6, 7). Defects in Mus308 or POLQ confer hypersensitivity to various DNA-damaging agents (7–9). Both mus308 and POLQ also encode an N-terminal helicase-like domain (10, 11). A third member of this gene family, HELQ, encodes a helicase domain similar to that of POLQ/Mus308 (Fig. 1A) (12). HELQ interacts with ataxia telangiectasia and Rad3-related (ATR) and with homologous recombination-related RAD51 paralogs and participates in DNA cross-link resistance in human cells (13–15).

Bottom Line: Consistent with this, injection of POLN-specific morpholino antisense oligonucleotides did not interfere with zebrafish embryonic development.These properties are conserved with the human enzyme.Although the physiological function of pol ν remains to be clarified, this study uncovers distinctive aspects of its expression control and evolutionarily conserved properties of this DNA polymerase.

View Article: PubMed Central - PubMed

Affiliation: From the Department of Epigenetics and Molecular Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, Texas 78957, the University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, ktakata@mdanderson.org.

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Related in: MedlinePlus