Schwaiger H, Hirsch-Kauffmann M, Schweiger M
Eur J Cell Biol. 1986 Aug;41(2):352-5.
Fibroblasts from patients with Cockayne Syndrome (CS) are hypersensitive to UV light. DNA repair was analyzed in these cells by sedimentation behaviour of DNA nucleoids in sucrose gradients and compared to normal control cells. The initiation of repair, the incision of the DNA strand next to the UV lesion appeared to be normal. The rejoining of DNA stretches, however, is retarded in CS cells. DNA repair synthesis of UV damages was measured by autoradiography of [14C]thymidine incorporation into resting cells. Up to 4 h the DNA repair synthesis was comparable with normal cells. From 4 to 7 h the incorporation of radioactive precursors declined in CS cells. Besides a defective DNA polymerase this could be due to accelerated excorporation of radioactive nucleotides as a consequence of delayed ligation. In ligation the enzyme itself could be affected as well as its activation by ADP-ribosylation. Nicotine adenine dinucleotide (NAD+) is needed for the ADP ribosylation process. The cellular NAD+ content, however, was found to be the same in normal and in CS fibroblasts. Increase of the extracellular NAD+ supply accelerated the rejoining of UV damaged DNA in CS cells.
科凯恩综合征（CS）患者的成纤维细胞对紫外线高度敏感。通过蔗糖梯度中DNA核小体的沉降行为对这些细胞中的DNA修复进行了分析，并与正常对照细胞进行了比较。修复的起始，即紫外线损伤旁DNA链的切割似乎是正常的。然而，CS细胞中DNA片段的重新连接受到阻碍。通过将[14C]胸苷掺入静息细胞的放射自显影法来测量紫外线损伤的DNA修复合成。长达4小时，DNA修复合成与正常细胞相当。从4到7小时，CS细胞中放射性前体的掺入量下降。除了DNA聚合酶缺陷外，这可能是由于连接延迟导致放射性核苷酸加速外排所致。在连接过程中，酶本身及其通过ADP-核糖基化的激活都可能受到影响。ADP-核糖基化过程需要烟酰胺腺嘌呤二核苷酸（NAD+）。然而，发现正常和CS成纤维细胞中的细胞NAD+含量相同。增加细胞外NAD+供应可加速CS细胞中紫外线损伤DNA的重新连接。
