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Int. J. Mol. Sci. 2017, 18(7), 1562; doi:10.3390/ijms18071562

DNA2—An Important Player in DNA Damage Response or Just Another DNA Maintenance Protein?

1
Department of Orthodontics, Medical University of Lodz, 92-216 Lodz, Poland
2
Department of Pediatric Dentistry, Medical University of Lodz, 92-216 Lodz, Poland
3
Department of Molecular Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
*
Author to whom correspondence should be addressed.
Received: 27 June 2017 / Revised: 13 July 2017 / Accepted: 17 July 2017 / Published: 18 July 2017
(This article belongs to the Special Issue DNA Injury and Repair Systems)
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Abstract

The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM). In mitochondria, DNA2 can facilitate primer removal during strand-displacement replication. DNA2 is involved in DNA double strand (DSB) repair, in which it is complexed with BLM, RPA and MRN for DNA strand resection required for homologous recombination repair. DNA2 can be a major protein involved in the repair of complex DNA damage containing a DSB and a 5′ adduct resulting from a chemical group bound to DNA 5′ ends, created by ionizing radiation and several anticancer drugs, including etoposide, mitoxantrone and some anthracyclines. The role of DNA2 in telomere end maintenance and cell cycle regulation suggests its more general role in keeping genomic stability, which is impaired in cancer. Therefore DNA2 can be an attractive target in cancer therapy. This is supported by enhanced expression of DNA2 in many cancer cell lines with oncogene activation and premalignant cells. Therefore, DNA2 can be considered as a potential marker, useful in cancer therapy. DNA2, along with PARP1 inhibition, may be considered as a potential target for inducing synthetic lethality, a concept of killing tumor cells by targeting two essential genes. View Full-Text
Keywords: DNA2; DNA replication; DNA repair; Okazaki fragment maturation; DNA end resection; homologous recombination repair; flap endonuclease DNA2; DNA replication; DNA repair; Okazaki fragment maturation; DNA end resection; homologous recombination repair; flap endonuclease
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Pawłowska, E.; Szczepanska, J.; Blasiak, J. DNA2—An Important Player in DNA Damage Response or Just Another DNA Maintenance Protein? Int. J. Mol. Sci. 2017, 18, 1562.

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