Boulikas T
Institute of Molecular Medical Sciences, Palo Alto, California 94306, USA.
Anticancer Res. 1996 Jan-Feb;16(1):225-42.
A great deal of the energy and time of a cell is invested in DNA repair activities. The first step in DNA repair pathways is recognition of the lesion on the DNA. The classical lesion-recognizing proteins interact with other repair proteins to form multiprotein complexes most notable of which are those that function in Nucleotide Excision Repair (NER). Proteins involved in lesion recognition include HMG1 and 2 recognizing cisplatin adducts but also maintaining active nucleosome structures and interacting with loops in cruciforms; HMG-box nuclear proteins; XPA and XPC lacking in xeroderma pigmentosum patients and involved in lesion recognition during NER; p53 recognizing strand breaks and insertion/deletion mismatches and causing arrest in the cell cycle; MSH2 mismatch repair protein identified as the human colon cancer gene product; and others including the transcription factor YB-1 that binds to depurinated DNA with a higher affinity compared with undamaged DNA. Other type of lesion-recognizing proteins are also repair enzymes like the O(6)-methylguanine-DNA methyltransferase and DNA glycosylases. Lesion recognition is an important process and might be the rate-limiting step in the overall repair process.
细胞的大量能量和时间都投入到了DNA修复活动中。DNA修复途径的第一步是识别DNA上的损伤。经典的损伤识别蛋白与其他修复蛋白相互作用形成多蛋白复合物，其中最显著的是那些在核苷酸切除修复（NER）中起作用的复合物。参与损伤识别的蛋白质包括识别顺铂加合物但也维持活性核小体结构并与十字形结构中的环相互作用的HMG1和2；HMG盒核蛋白；着色性干皮病患者缺乏且参与NER过程中损伤识别的XPA和XPC；识别链断裂和插入/缺失错配并导致细胞周期停滞的p53；被鉴定为人类结肠癌基因产物的错配修复蛋白MSH2；以及其他一些蛋白，包括与未受损DNA相比，与脱嘌呤DNA具有更高亲和力的转录因子YB-1。其他类型的损伤识别蛋白也是修复酶，如O(6)-甲基鸟嘌呤-DNA甲基转移酶和DNA糖基化酶。损伤识别是一个重要过程，可能是整个修复过程中的限速步骤。
