Orren D K, Petersen L N, Bohr V A
Laboratory of Molecular Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Mol Biol Cell. 1997 Jun;8(6):1129-42. doi: 10.1091/mbc.8.6.1129.
We used genetically related Chinese hamster ovary cell lines proficient or deficient in DNA repair to determine the direct role of UV-induced DNA photoproducts in inhibition of DNA replication and in induction of G2 arrest and apoptosis. UV irradiation of S-phase-synchronized cells causes delays in completion of the S-phase sometimes followed by an extended G2 arrest and apoptosis. The effects of UV irradiation during the S-phase on subsequent cell cycle progression are magnified in repair-deficient cells, indicating that these effects are initiated by persistent DNA damage and not by direct UV activation of signal transduction pathways. Moreover, among the lesions introduced by UV irradiation, persistence of (6-4) photoproducts inhibits DNA synthesis much more than persistence of cyclobutane pyrimidine dimers (which appear to be efficiently bypassed by the DNA replication apparatus). Apoptosis begins approximately 24 h after UV irradiation of S-phase-synchronized cells, occurs to a greater extent in repair-deficient cells, and correlates well with the inability to escape from an extended late S-phase-G2 arrest. We also find that nucleotide excision repair activity (including its coupling to transcription) is similar in the S-phase to what we have previously measured in G1 and G2.
我们使用了在DNA修复方面 proficient 或 deficient 的基因相关中国仓鼠卵巢细胞系，以确定紫外线诱导的DNA光产物在抑制DNA复制、诱导G2期阻滞和凋亡中的直接作用。对处于S期同步化的细胞进行紫外线照射会导致S期完成延迟，有时随后会出现延长的G2期阻滞和凋亡。在S期进行紫外线照射对后续细胞周期进程的影响在修复缺陷细胞中会放大，这表明这些影响是由持续性DNA损伤引发的，而非由信号转导途径的直接紫外线激活引发。此外，在紫外线照射引入的损伤中，（6-4）光产物的持续性对DNA合成的抑制作用远大于环丁烷嘧啶二聚体的持续性（DNA复制装置似乎能有效绕过环丁烷嘧啶二聚体）。对处于S期同步化的细胞进行紫外线照射后约24小时开始凋亡，在修复缺陷细胞中凋亡程度更大，且与无法从延长的S期末期-G2期阻滞中逃脱密切相关。我们还发现，核苷酸切除修复活性（包括其与转录的偶联）在S期与我们之前在G1期和G2期测量的结果相似。 注：原文中proficient or deficient 处，proficient 直译为精通、熟练等，但结合语境这里可能是指有DNA修复能力（ proficient in DNA repair）和缺乏DNA修复能力（deficient in DNA repair） ，暂保留英文未译出更准确中文表述。
