Mutually regulated expression of caspase-activated DNase and its inhibitor for apoptotic DNA fragmentation

Nagase, Hiroko; Fukuyama, Hidehiro; Tanaka, Masato; Kawane, Kohki; Nagata, Shinji

doi:10.1038/sj.cdd.4401139

Cited by 27 publications

(27 citation statements)

References 14 publications

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“…2B). This fact is in agreement with previous data establishing the role of ICAD L , but not ICAD S , as a chaperone for DFF40/CAD (33) and, therefore, regulating the expression of the endonuclease (34). Regardless of the effect provoked on the aspect of the nuclei, none of the siRNAs designed avoided the STP-induced DNA degradation profile into high molecular weight (HMW) fragments (supplemental Fig.…”

Section: Dff40/cad Is Required For Stage II Nuclear Morphologysupporting

confidence: 92%

Chromatin Collapse during Caspase-dependent Apoptotic Cell Death Requires DNA Fragmentation Factor, 40-kDa Subunit-/Caspase-activated Deoxyribonuclease-mediated 3′-OH Single-strand DNA Breaks

Iglesias-Guimarais

Gil-Guiñón

Sánchez-Osuna

et al. 2013

Journal of Biological Chemistry

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Background: Apoptotic nuclear morphology can occur independently of DFF40/CAD-mediated DNA fragmentation. Results: DFF40/CAD induces 3Ј-OH single-strand DNA nicks/breaks and nuclear collapse during caspase-dependent apoptosis. Conclusion: Caspase-dependent apoptotic nuclear collapse is prompted by DFF40/CAD-mediated single-strand DNA damage. Significance: The knowledge of how apoptotic nuclear collapse occurs should be relevant to understand the final steps of cell demise and its influence on the cellular environment.

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Section: Dff40/cad Is Required For Stage II Nuclear Morphologysupporting

confidence: 92%

Chromatin Collapse during Caspase-dependent Apoptotic Cell Death Requires DNA Fragmentation Factor, 40-kDa Subunit-/Caspase-activated Deoxyribonuclease-mediated 3′-OH Single-strand DNA Breaks

Iglesias-Guimarais

Gil-Guiñón

Sánchez-Osuna

et al. 2013

Journal of Biological Chemistry

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“…Its gene product is complexed with an inhibitor encoded by DFFA in vivo. Upon apoptosis induction, caspase cleaves the inhibitor and releases DFFB from the complex to enter into nuclei to degrade chromosomal DNA (Nagase et al, 2003). No somatic mutations of DFFB were detected in 41 neuroblastomas examined (Judson et al, 2000).…”

Section: Discussionmentioning

confidence: 97%

Identification of two contiguous minimally deleted regions on chromosome 1p36.31–p36.32 in oligodendroglial tumours

Dong

Pang

et al. 2004

Br J Cancer

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Loss of the short arm of chromosome 1 is a hallmark of oligodendroglial tumours (OTs). Deletion mapping studies in OTs have revealed multiple commonly deleted regions on chromosome 1p, suggesting that there are more than one tumour suppressor gene. To map critical deletion regions on 1p, a series of 25 OTs were examined for loss of heterozygosity (LOH) on 19 polymorphic markers across the 1p arm using microsatellite analysis. Our study revealed that 60% of tumours had LOH of all informative markers on 1p and identified one tumour showing LOH at telomeric markers only. Since this deletion region lies in one of the critical deletion intervals defined previously, we then screened another series of 27 OTs specifically at 1p36.3 for LOH using nine polymorphic markers. A total of 12% (six out of 52) of tumours were found to carry interstitial deletions. The allelic status and the deletion breakpoints in these tumours with interstitial deletion were further verified by fluorescent in situ hybridisation. The small overlapping intervals facilitated the delineation of two contiguous minimally deleted regions of 0.76 Mb, defined by D1S468 and D1S2845, and of 0.41 Mb, bound by D1S2893 and D1S1608, on 1p36.31 -36.32. Based on current reference human genome sequence these deletion regions have been sequenced almost to entirety and contain eight annotated genes. TP73, DFFB and SHREW1 are the only known genes located in these deletion regions, while the others are uncharacterised novel genes. In conclusion, our study has narrowed down the critical tumour suppressor loci on 1p36.3, in which two minimally deleted regions are mapped, and markedly reduced the number of candidate genes to be screened for their involvement in OT development.

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“…32,37,40 In addition to the regulation of CAD by ICAD-L, we recently found that the expression of ICAD-L but not ICAD-S is regulated by CAD at the post-translational level, suggesting that their expression is mutually regulated. 104 No specific function has been assigned to ICAD-S, and it is probably dispensable in most if not all species, as has been shown in Drosophila. 48 In this regard, results by Chen et al 49 indicating that rat and mouse tissues express only ICAD-S are difficult to explain.…”

Section: Inhibitor Of Cad (Icad Dff45)mentioning

confidence: 99%

Degradation of chromosomal DNA during apoptosis

et al. 2003

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Apoptosis is often accompanied by degradation of chromosomal DNA. CAD, caspase-activated DNase, was identified in 1998 as a DNase that is responsible for this process. In the last several years, mice deficient in the CAD system have been generated. Studies with these mice indicated that apoptotic DNA degradation occurs in two different systems. In one, the DNA fragmentation is carried out by CAD in the dying cells and in the other, by lysosomal DNase II after the dying cells are phagocytosed. Several other endonucleases have also been suggested as candidate effectors for the apoptotic degradation of chromosomal DNA. In this review, we will discuss the mechanism and role of DNA degradation during apoptosis.

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Mutually regulated expression of caspase-activated DNase and its inhibitor for apoptotic DNA fragmentation

Cited by 27 publications

References 14 publications

Chromatin Collapse during Caspase-dependent Apoptotic Cell Death Requires DNA Fragmentation Factor, 40-kDa Subunit-/Caspase-activated Deoxyribonuclease-mediated 3′-OH Single-strand DNA Breaks

Chromatin Collapse during Caspase-dependent Apoptotic Cell Death Requires DNA Fragmentation Factor, 40-kDa Subunit-/Caspase-activated Deoxyribonuclease-mediated 3′-OH Single-strand DNA Breaks

Identification of two contiguous minimally deleted regions on chromosome 1p36.31–p36.32 in oligodendroglial tumours

Degradation of chromosomal DNA during apoptosis

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