Apoptosis induced DNA fragmentation

DNA fragmentation in response to apoptotic signals is achieved, in part, through the activity of apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) (reviewed in Widlak and Garrard, 2005). In non-apoptotic cells, DFF is a nuclear heterodimer consisting of a 45 kD chaperone and inhibitor subunit (DFF45)/inhibitor of CAD (ICAD-L)] and a 40 kD nuclease subunit (DFF40/CAD)( Liu et al. 1997, 1998; Enari et al. 1998). During apoptosis, activated caspase-3 or -7 cleave DFF45/ICAD releasing active DFF40/CAD nuclease. The activity of DFF is tightly controlled at multiple stages. During translation, DFF45/ICAD, Hsp70, and Hsp40 proteins play a role in insuring the appropriate folding of DFF40 during translation(Sakahira and Nagata, 2002). The nuclease activity of DFF40 is enhanced by the chromosomal proteins histone H1, Topoisomerase II and HMGB1/2(Widlak et al., 2000). In addition, the inhibitors (DFF45/35; ICAD-S/L) are produced in stoichiometric excess (Widlak et al., 2003).

细胞凋亡信号引发的DNA断裂部分通过凋亡核酸酶的活性实现，这些凋亡核酸酶被称为DNA断裂因子（DFF）或caspase激活的DNase（CAD）（参见Widlak和Garrard，2005年综述）。在非凋亡细胞中，DFF是一种由45 kD的伴侣和抑制子亚基（DFF45）/CAD抑制子（ICAD-L）与40 kD的核酸酶亚基（DFF40/CAD）组成的核异源二聚体（刘等，1997年，1998年；Enari等，1998年）。在细胞凋亡过程中，激活的caspase-3或-7切割DFF45/ICAD，释放活性DFF40/CAD核酸酶。DFF的活性在多个阶段受到严格调控。在翻译过程中，DFF45/ICAD、Hsp70和Hsp40蛋白确保DFF40在翻译过程中的正确折叠（Sakahira和Nagata，2002年）。DFF40的核酸酶活性通过染色质蛋白组蛋白H1、拓扑异构酶II和HMGB1/2得到增强（Widlak等，2000年）。此外，抑制子（DFF45/35；ICAD-S/L）以化学计量过剩的形式产生（Widlak等，2003年）。