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

摘要: Abstract 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), the progression of S phase cycle is accompanied by its expression. APEX2-null mice exhibit severe dyslymphopoiesis in thymus as well moderate dyshematopoiesis growth retardation. Comparative gene expression profiling wild-type using an oligonucleotide microarray revealed that has significantly altered profiles, reflecting populations thymocytes. Beyond these populations, exhibits significant alterations genes involved DNA replication, recombination repair, including Apex1, Exo1 Fen1 master for damage response, such E2f1, Chek1, proapoptotic genes. We therefore examined extent strand breakage, found both single-strand breaks detected comets double-strand γH2AX foci were higher frequency most thymocytes compared to This was increased PCNA phosphorylation p53 at Ser23 a lesser extent, Ser18. The present study clearly demonstrates lymphocytes have breaks, indicating may play important role(s) during their generation and/or repair.