Woynarowski J M, Beerman T A
Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo, NY 14263.
Biochim Biophys Acta. 1989 Jan 23;1007(1):116-9. doi: 10.1016/0167-4781(89)90139-5.
This study determined whether nascent chromatin in nuclei from leukemia L1210 cells constitutes a preferential target for bleomycin. No differences were seen in fragmentation of nascent and bulk DNA as judged by DNA double-stranded cleavage and the release of acid-soluble material or subnucleosomal (under 8 S) fragments. In contrast, bleomycin-induced chromatin aggregation (Woynarowski, J.M., Gawron, L.S. and Beerman, T.A. (1987) Biochim. Biophys. Acta 910, 149-156) occurred preferentially in nascent chromatin as indicated by a retarded solubilization of nascent chromatin and generation of a fast-sedimenting material (above 45 S) in the sedimentation profiles of drug-released nascent chromatin. This preferential aggregation disappeared completely when chromatin became older than 10 min. The drug aggregation activity did not distinguish nascent and mature presolubilized oligonucleosomes. The results suggest that bleomycin recognizes higher-order structures of nascent chromatin.
本研究确定白血病L1210细胞核中的新生染色质是否构成博来霉素的优先作用靶点。通过DNA双链断裂以及酸溶性物质或亚核小体（小于8S）片段的释放来判断，新生DNA和总体DNA的片段化未见差异。相比之下，如新生染色质溶解延迟以及药物释放的新生染色质沉降图谱中产生快速沉降物质（大于45S）所示，博来霉素诱导的染色质聚集（Woynarowski, J.M., Gawron, L.S.和Beerman, T.A. (1987) Biochim. Biophys. Acta 910, 149 - 156）优先发生在新生染色质中。当染色质形成超过10分钟时，这种优先聚集完全消失。药物聚集活性无法区分新生和成熟的预溶解寡核小体。结果表明，博来霉素识别新生染色质的高级结构。
