Su Dian G T, Fang Huafeng, Gross Michael L, Taylor John-Stephen A
Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12861-6. doi: 10.1073/pnas.0902386106. Epub 2009 Jul 23.
The unusual structural forms of telomere DNA, which protect the ends of chromosomes during replication, may render it vulnerable to unprecedented photodamage, possibly involving nonadjacent bases that are made proximate by folding. The G-quadruplex for the human telomere sequence consisting of a repeating d(TTAGGG) is one unusual form. Tel22, d[AGGG(TTAGGG)(3)], forms a basket structure in the presence of Na(+) and may form multiple equilibrating structures in the presence of K(+) with hybrid-type structures predominating. UVB irradiation of d[AGGG(TTAGGG)(3)] in the presence of Na(+) results in a cis,syn thymine dimer between two adjacent Ts in a TTA loop and a mixture of nonadjacent anti thymine dimers between various loops. Irradiation in the presence of K(+), however, produces, in addition to these same products, a large amount of specific anti thymine dimers formed between either T in loop 1 and the central T in loop 3. These latter species were not observed in the presence of Na(+). Interloop-specific anti thymine dimers are incompatible with hybrid-type structures, but could arise from a chair or basket-type structure or from triplex intermediates involved in interconverting these structures. If these unique nonadjacent anti thymine dimer photoproducts also form in vivo, they would constitute a previously unrecognized type of DNA photodamage that may interfere with telomere replication and present a unique challenge to DNA repair. Furthermore, these unusual anti photoproducts may be used to establish the presence of G-quadruplex or quadruplex-like structures in vivo.
端粒DNA的异常结构形式在复制过程中保护染色体末端，可能使其易受前所未有的光损伤，这可能涉及通过折叠而靠近的非相邻碱基。由重复的d(TTAGGG)组成的人类端粒序列的G-四链体就是一种异常形式。Tel22，即d[AGGG(TTAGGG)(3)]，在存在Na(+)时形成篮状结构，在存在K(+)时可能形成多种平衡结构，其中以杂合型结构为主。在存在Na(+)的情况下，对d[AGGG(TTAGGG)(3)]进行UVB照射会导致TTA环中两个相邻T之间形成顺式、反式胸腺嘧啶二聚体，以及不同环之间非相邻反式胸腺嘧啶二聚体的混合物。然而，在存在K(+)的情况下进行照射，除了这些相同的产物外，还会在环1中的任何一个T与环3中的中心T之间形成大量特定的反式胸腺嘧啶二聚体。在存在Na(+)的情况下未观察到后一种产物。环间特异性反式胸腺嘧啶二聚体与杂合型结构不相容，但可能源于椅型或篮型结构，或源于参与这些结构相互转化的三链中间体。如果这些独特的非相邻反式胸腺嘧啶二聚体光产物也在体内形成，则它们将构成一种以前未被认识的DNA光损伤类型，可能会干扰端粒复制，并给DNA修复带来独特挑战。此外，这些异常的光产物可用于确定体内G-四链体或类似四链体结构的存在。
