Human Dna2 is a nuclear and mitochondrial DNA maintenance protein

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Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. / Duxin, Julien P; Dao, Benjamin; Martinsson, Peter; Rajala, Nina; Guittat, Lionel; Campbell, Judith L; Spelbrink, Johannes N; Stewart, Sheila A.

In: Molecular and Cellular Biology, Vol. 29, No. 15, 08.2009, p. 4274-82.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Duxin, JP, Dao, B, Martinsson, P, Rajala, N, Guittat, L, Campbell, JL, Spelbrink, JN & Stewart, SA 2009, 'Human Dna2 is a nuclear and mitochondrial DNA maintenance protein', Molecular and Cellular Biology, vol. 29, no. 15, pp. 4274-82. https://doi.org/10.1128/MCB.01834-08

APA

Duxin, J. P., Dao, B., Martinsson, P., Rajala, N., Guittat, L., Campbell, J. L., Spelbrink, J. N., & Stewart, S. A. (2009). Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. Molecular and Cellular Biology, 29(15), 4274-82. https://doi.org/10.1128/MCB.01834-08

Vancouver

Duxin JP, Dao B, Martinsson P, Rajala N, Guittat L, Campbell JL et al. Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. Molecular and Cellular Biology. 2009 Aug;29(15):4274-82. https://doi.org/10.1128/MCB.01834-08

Author

Duxin, Julien P ; Dao, Benjamin ; Martinsson, Peter ; Rajala, Nina ; Guittat, Lionel ; Campbell, Judith L ; Spelbrink, Johannes N ; Stewart, Sheila A. / Human Dna2 is a nuclear and mitochondrial DNA maintenance protein. In: Molecular and Cellular Biology. 2009 ; Vol. 29, No. 15. pp. 4274-82.

Bibtex

@article{2d9fe2524a9c4c0f98042e0fb6c204c0,
title = "Human Dna2 is a nuclear and mitochondrial DNA maintenance protein",
abstract = "Dna2 is a highly conserved helicase/nuclease that in yeast participates in Okazaki fragment processing, DNA repair, and telomere maintenance. Here, we investigated the biological function of human Dna2 (hDna2). Immunofluorescence and biochemical fractionation studies demonstrated that hDna2 was present in both the nucleus and the mitochondria. Analysis of mitochondrial hDna2 revealed that it colocalized with a subfraction of DNA-containing mitochondrial nucleoids in unperturbed cells. Upon the expression of disease-associated mutant forms of the mitochondrial Twinkle helicase which induce DNA replication pausing/stalling, hDna2 accumulated within nucleoids. RNA interference-mediated depletion of hDna2 led to a modest decrease in mitochondrial DNA replication intermediates and inefficient repair of damaged mitochondrial DNA. Importantly, hDna2 depletion also resulted in the appearance of aneuploid cells and the formation of internuclear chromatin bridges, indicating that nuclear hDna2 plays a role in genomic DNA stability. Together, our data indicate that hDna2 is similar to its yeast counterpart and is a new addition to the growing list of proteins that participate in both nuclear and mitochondrial DNA maintenance.",
keywords = "Blotting, Western, Cell Line, Cell Nucleus, Cytoplasm, DNA Damage, DNA Helicases, DNA Repair, DNA Replication, DNA, Mitochondrial, Fluorescent Antibody Technique, HeLa Cells, Humans, Immunoprecipitation, Microscopy, Confocal, Mitochondria, Mitochondrial Proteins, Mutation, RNA Interference, Journal Article",
author = "Duxin, {Julien P} and Benjamin Dao and Peter Martinsson and Nina Rajala and Lionel Guittat and Campbell, {Judith L} and Spelbrink, {Johannes N} and Stewart, {Sheila A}",
year = "2009",
month = aug,
doi = "10.1128/MCB.01834-08",
language = "English",
volume = "29",
pages = "4274--82",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "15",

}

RIS

TY - JOUR

T1 - Human Dna2 is a nuclear and mitochondrial DNA maintenance protein

AU - Duxin, Julien P

AU - Dao, Benjamin

AU - Martinsson, Peter

AU - Rajala, Nina

AU - Guittat, Lionel

AU - Campbell, Judith L

AU - Spelbrink, Johannes N

AU - Stewart, Sheila A

PY - 2009/8

Y1 - 2009/8

N2 - Dna2 is a highly conserved helicase/nuclease that in yeast participates in Okazaki fragment processing, DNA repair, and telomere maintenance. Here, we investigated the biological function of human Dna2 (hDna2). Immunofluorescence and biochemical fractionation studies demonstrated that hDna2 was present in both the nucleus and the mitochondria. Analysis of mitochondrial hDna2 revealed that it colocalized with a subfraction of DNA-containing mitochondrial nucleoids in unperturbed cells. Upon the expression of disease-associated mutant forms of the mitochondrial Twinkle helicase which induce DNA replication pausing/stalling, hDna2 accumulated within nucleoids. RNA interference-mediated depletion of hDna2 led to a modest decrease in mitochondrial DNA replication intermediates and inefficient repair of damaged mitochondrial DNA. Importantly, hDna2 depletion also resulted in the appearance of aneuploid cells and the formation of internuclear chromatin bridges, indicating that nuclear hDna2 plays a role in genomic DNA stability. Together, our data indicate that hDna2 is similar to its yeast counterpart and is a new addition to the growing list of proteins that participate in both nuclear and mitochondrial DNA maintenance.

AB - Dna2 is a highly conserved helicase/nuclease that in yeast participates in Okazaki fragment processing, DNA repair, and telomere maintenance. Here, we investigated the biological function of human Dna2 (hDna2). Immunofluorescence and biochemical fractionation studies demonstrated that hDna2 was present in both the nucleus and the mitochondria. Analysis of mitochondrial hDna2 revealed that it colocalized with a subfraction of DNA-containing mitochondrial nucleoids in unperturbed cells. Upon the expression of disease-associated mutant forms of the mitochondrial Twinkle helicase which induce DNA replication pausing/stalling, hDna2 accumulated within nucleoids. RNA interference-mediated depletion of hDna2 led to a modest decrease in mitochondrial DNA replication intermediates and inefficient repair of damaged mitochondrial DNA. Importantly, hDna2 depletion also resulted in the appearance of aneuploid cells and the formation of internuclear chromatin bridges, indicating that nuclear hDna2 plays a role in genomic DNA stability. Together, our data indicate that hDna2 is similar to its yeast counterpart and is a new addition to the growing list of proteins that participate in both nuclear and mitochondrial DNA maintenance.

KW - Blotting, Western

KW - Cell Line

KW - Cell Nucleus

KW - Cytoplasm

KW - DNA Damage

KW - DNA Helicases

KW - DNA Repair

KW - DNA Replication

KW - DNA, Mitochondrial

KW - Fluorescent Antibody Technique

KW - HeLa Cells

KW - Humans

KW - Immunoprecipitation

KW - Microscopy, Confocal

KW - Mitochondria

KW - Mitochondrial Proteins

KW - Mutation

KW - RNA Interference

KW - Journal Article

U2 - 10.1128/MCB.01834-08

DO - 10.1128/MCB.01834-08

M3 - Journal article

C2 - 19487465

VL - 29

SP - 4274

EP - 4282

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 15

ER -

ID: 186871984