Human DNA2 Is a Mitochondrial Nuclease/Helicase for Efficient Processing of DNA Replication and Repair Intermediates

Li Zheng, Mian Zhou, Zhigang Guo, Huiming Lu, Limin Qian, Huifang Dai, Junzhuan Qiu, Elena Yakubovskaya, Daniel F. Bogenhagen, Bruce Demple, Binghui Shen

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

DNA2, a helicase/nuclease family member, plays versatile roles in processing DNA intermediates during DNA replication and repair. Yeast Dna2 (yDna2) is essential in RNA primer removal during nuclear DNA replication and is important in repairing UV damage, base damage, and double-strand breaks. Our data demonstrate that, surprisingly, human DNA2 (hDNA2) does not localize to nuclei, as it lacks a nuclear localization signal equivalent to that present in yDna2. Instead, hDNA2 migrates to the mitochondria, interacts with mitochondrial DNA polymerase γ, and significantly stimulates polymerase activity. We further demonstrate that hDNA2 and flap endonuclease 1 synergistically process intermediate 5′ flap structures occurring in DNA replication and long-patch base excision repair (LP-BER) in mitochondria. Depletion of hDNA2 from a mitochondrial extract reduces its efficiency in RNA primer removal and LP-BER. Taken together, our studies illustrate an evolutionarily diversified role of hDNA2 in mitochondrial DNA replication and repair in a mammalian system.

Original languageEnglish (US)
Pages (from-to)325-336
Number of pages12
JournalMolecular Cell
Volume32
Issue number3
DOIs
StatePublished - Nov 7 2008

Fingerprint

DNA Replication
DNA Repair
Mitochondrial DNA
Mitochondria
Flap Endonucleases
Yeasts
Nuclear Localization Signals
DNA-Directed DNA Polymerase
DNA
RNA primers

Keywords

  • DNA
  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Human DNA2 Is a Mitochondrial Nuclease/Helicase for Efficient Processing of DNA Replication and Repair Intermediates. / Zheng, Li; Zhou, Mian; Guo, Zhigang; Lu, Huiming; Qian, Limin; Dai, Huifang; Qiu, Junzhuan; Yakubovskaya, Elena; Bogenhagen, Daniel F.; Demple, Bruce; Shen, Binghui.

In: Molecular Cell, Vol. 32, No. 3, 07.11.2008, p. 325-336.

Research output: Contribution to journalArticle

Zheng, L, Zhou, M, Guo, Z, Lu, H, Qian, L, Dai, H, Qiu, J, Yakubovskaya, E, Bogenhagen, DF, Demple, B & Shen, B 2008, 'Human DNA2 Is a Mitochondrial Nuclease/Helicase for Efficient Processing of DNA Replication and Repair Intermediates', Molecular Cell, vol. 32, no. 3, pp. 325-336. https://doi.org/10.1016/j.molcel.2008.09.024
Zheng, Li ; Zhou, Mian ; Guo, Zhigang ; Lu, Huiming ; Qian, Limin ; Dai, Huifang ; Qiu, Junzhuan ; Yakubovskaya, Elena ; Bogenhagen, Daniel F. ; Demple, Bruce ; Shen, Binghui. / Human DNA2 Is a Mitochondrial Nuclease/Helicase for Efficient Processing of DNA Replication and Repair Intermediates. In: Molecular Cell. 2008 ; Vol. 32, No. 3. pp. 325-336.
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