Ramel C
Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):781-9. doi: 10.1289/ehp.97105s4781.
While the faithful transmission of genetic information requires a fidelity and stability of DNA that is involved in translation into proteins, it has become evident that a large part of noncoding DNA is organized in repeated sequences, which often exhibit a pronounced instability and dynamics. This applies both to longer repeated sequences, minisatellites (about 10-100 base pairs), and microsatellites (mostly 2-4 base pairs). Although these satellite DNAs are abundantly distributed in all kinds of organisms, no clear function has been discerned for them. However, extension of trinucleotide microsatellite sequences has been associated with several severe human disorders, such as Fragile X syndrome and Huntington's disease. Rare alleles of a minisatellite sequence have been reported to be associated with the ras oncogene leading to an increased risk for several human cancers. A dynamic behavior of repeated DNA sequences also applies to telomeres, constituting the ends of the chromosomes. Repeated DNA sequences protect the chromosome ends from losing coding sequences at cell divisions. The telomeres are maintained by the enzyme telomerase. Somatic cells, however, lose telomerase function and gradually die. Cancer cells have activated telomerase and therefore they acquire immortality.
虽然遗传信息的准确传递需要参与蛋白质翻译的DNA具有保真度和稳定性,但很明显,很大一部分非编码DNA是由重复序列组成的,这些重复序列往往表现出明显的不稳定性和动态性。这既适用于较长的重复序列,如小卫星(约10 - 100个碱基对)和微卫星(大多为2 - 4个碱基对)。尽管这些卫星DNA在各种生物体中广泛分布,但尚未发现它们有明确的功能。然而,三核苷酸微卫星序列的延伸与几种严重的人类疾病有关,如脆性X综合征和亨廷顿舞蹈症。据报道,一种小卫星序列的罕见等位基因与ras癌基因有关,会增加患几种人类癌症的风险。重复DNA序列的动态行为也适用于构成染色体末端的端粒。重复DNA序列可保护染色体末端在细胞分裂时不丢失编码序列。端粒由端粒酶维持。然而,体细胞会失去端粒酶功能并逐渐死亡。癌细胞激活了端粒酶,因此获得了永生。