Endonuclease Activation and Chromosomal DNA Fragmentation during Apoptosis in Leukemia Cells

Abstract

Apoptotic endonuclease is a key enzyme that mediates regulated DNA fragmentation and chromatin condensation in response to apoptotic signals such as the Fas ligand, ionizing radiation, and anticancer agents. An endonuclease that is activated specifically by caspase-3 has been identified in humans and mice. The human gene for this protein has been termed DFF40 (DNA fragmentation factor, 40-kd subunit) or caspase-activated nuclease (CPAN), whereas the mouse homologue has been named caspase-activated deoxyribonuclease (CAD). Although CAD/DFF40 is known as a major apoptotic nuclease, mice lacking inhibitor of CAD (ICAD) (also known as DFF45) are viable and still show DNA fragmentation, suggesting that alternative endonucleases play an important role during apoptosis. Endonuclease G has been reported to possibly be responsible for DNA fragmentation in various cells during apoptosis. Furthermore, we also have found that apurinic/apyrimidinic endonuclease 1 (Ape1) and its N-terminal-truncated form (AN34) are involved in DNA fragmentation during apoptosis in leukemia cells. In this review, we describe the features of several endonucleases that are involved in the apoptosis of human leukemia cells. Apoptotic endonuclease may vary among different leukemia cell types.

Role of carbohydrate moiety of bleomycin‐A2 in caspase‐3 activation and internucleosomal chromatin fragmentation in apoptosis of laryngeal carcinoma cells

“…This endonuclease is a magnesiumdependent endonuclease DNA that specifically generates double-strand breaks with 3-hydroxyl ends. DFF40/CAD is activated by caspase-3 that cleaves the nuclease inhibitor DFF45/ ICAD (Beni et al, 1999;Widalk, 2000;Yoshida et al, 2006). Therefore, the absence of activation of caspase-3 in HEp-2 apoptotic cells treated with deglycoBLM-A2 may explain the absence of activation of the endonuclease DFF40/CAD responsible for the DNA ladder (Adriana et al, 2006;Kumiko et al, 2001;Widalk, 2000).…”

Hypoxia-induced human endonuclease G expression suppresses tumor growth in a xenograft model

“…hEndoG has been shown to digest both single strand RNA as well as DNA and functions during apoptosis. [14][15][16][17][18][19] It is normally sequestered between the inner and outer membranes of the mitochondria and is released with other apoptotic factors during apoptosis. In addition, we have incorporated a TLM 21 into the N-terminus of our chimeric protein to provide a possible bystander capability that can be tested in future applications.…”

“…14 Human endonuclease G is normally compartmentalized in the mitochondria and following its release into the cytoplasm, it can function in apoptotic processes. [15][16][17][18][19] The expression of this novel protein construct has been placed under the control of a conditional promoter, which consists of five HREs in tandem upstream of a minimal cytomegalovirus promoter. 20 In addition, we fused the coding sequence of the mature hEndoG (without the mitochondrial localization signal) to the coding sequence of the ODD domain of HIF-1a.…”

Curcumin Inhibits Cell Proliferation of Human Colorectal HCT116 Cells through Up-Regulation of Activating Transcription Factor 3 (ATF3)

“…DNA microarray실 험 결과, Table 3에서 보는 것과 같이 세포사멸과 관련된 유전 자들을 확인할 수 있었다. 이 중 가장 높은 발현 증가율을 보여 준 DFFB 유전자는 세포사멸 동안 DNA 분절과 염색체 응축을 촉진하는 것으로 알려져 있다 [20]. 이러한 연구결과는 curcumin에 의한 항 성장효과 혹은 세포사멸 현상은 ATF3 유전자 의 과대발현과 직접적인 관련이 있으며, 이러한 ATF3유전자 는 세포사멸과 관련된 유전자의 발현을 조절하는 것으로 생각 된다.…”