Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null thymus.

A second class II AP endonuclease, APEX2, possesses strong 3'-5' exonuclease and 3'-phosphodiesterase activities but only very weak AP-endonuclease activity. APEX2 associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. APEX2-null mice exhibit severe dyslymphopoiesis in thymus as well as moderate dyshematopoiesis and growth retardation.

Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice.

APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis.

Biological significance of the defense mechanisms against oxidative damage in nucleic acids caused by reactive oxygen species: from mitochondria to nuclei.

In mammalian cells, more than one genome in a single cell has to be maintained throughout the entire life of the cell, namely, one in the nucleus and the other in the mitochondria. The genomes and their precursor nucleotides are highly exposed to reactive oxygen species, which are inevitably generated as a result of the respiratory function in mitochondria. To counteract such oxidative damage in nucleic acids, cells are equipped with several defense mechanisms.

Characterization of the genomic structure and expression of the mouse Apex2 gene.

We isolated a mouse cDNA encoding APEX2 protein and demonstrated that APEX2 binds to PCNA. The level of Apex2 mRNA was high in the thymus, bone marrow, spleen, and kidney in adult mice. Apex2 consists of six exons and is flanked on the 3' end by Alas2 on X chromosome 63.