DNA2
Function
Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair: recruited by BLM and mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function.
Involvement in disease
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6
PEOA6
A disorder characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression.
None
The disease is caused by variants affecting the gene represented in this entry.
Seckel syndrome 8
SCKL8
A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.
None
The disease is caused by variants affecting the gene represented in this entry.
Rothmund-Thomson syndrome 4
RTS4
A form of Rothmund-Thomson syndrome, a disorder characterized by sparse hair, eyebrows and eyelashes, juvenile cataracts, and poikiloderma, a genodermatosis presenting with mottled pigmentation, telangiectasia and epidermal atrophy. Additional features are short stature, dysplastic nails, and skeletal and dental abnormalities. Inheritance is autosomal recessive. RTS4 patients also exhibit microcephaly and photosensitivity with bullae. Growth failure is severe, with some individuals showing signs of growth hormone or combined pituitary hormone deficiency.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Acetylated by EP300, leading to stimulate the 5'-3' endonuclease, the 5'-3' helicase and DNA-dependent ATPase activities, possibly by increasing DNA substrate affinity.
Sequence Similarities
Belongs to the DNA2/NAM7 helicase family.
Cellular localization
- Nucleus
- Mitochondrion
- Was initially reported to be exclusively mitochondrial (PubMed:18995831). However, it was later shown to localize both in mitochondrion and nucleus (PubMed:19487465).
Alternative names
DNA2L, KIAA0083, DNA2, DNA replication ATP-dependent helicase/nuclease DNA2, hDNA2, DNA replication ATP-dependent helicase-like homolog