Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats
Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats
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DOI：
10.1093/nar/gkm036
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发表时间：
2007-02-01
影响因子：
14.9
通讯作者：
Kurahashi, Hiroki
中科院分区：
文献类型：
--
作者：
Kogo, Hiroshi;Inagaki, Hidehito;Kurahashi, Hiroki
有一个正在形成的共识，即DNA的二级结构具有基因组不稳定性的潜力。富含AT的回文重复序列（Palindromic AT-rich repeats，PATRR）是在人类t（11;22）和t（17;22）易位的每一个断裂点上发现的特征性序列，分别命名为PATRR 22（类似于600 bp）、PATRR 11（类似于450 bp）和PATRR 17（类似于190 bp）。针对大小和对称性不同的各种PATRR，已经通过实验评估了体外二级结构形成倾向和体内不稳定性。在生理离子强度下，对于对称的PATRR 22最常观察到十字形结构，对于对称的PATRR 11较少观察到十字形结构，但对于其他PATRR则不常见。在野生型E.在大肠杆菌中，只有这两种PATRR经历了广泛的不稳定性，与人类中相对高的t（11;22）发病率一致。由此产生的缺失是publetin介导的结构特异性核酸内切酶SbcCD的中央切割，表明在体内的十字形构象的可能性。在PATRR 22的中心插入短间隔器大大减少了其在体外的十字形挤出和在体内的不稳定性。总之，十字形挤压倾向取决于PATRR的长度和中心对称性，并且可能决定导致人类复发性易位的不稳定性。
There is an emerging consensus that secondary structures of DNA have the potential for genomic instability. Palindromic AT-rich repeats (PATRRs) are a characteristic sequence identified at each breakpoint of the recurrent constitutional t(11;22) and t(17;22) translocations in humans, named PATRR22 (similar to 600 bp), PATRR11 (similar to 450 bp) and PATRR17 (similar to 190 bp). The secondary structure-forming propensity in vitro and the instability in vivo have been experimentally evaluated for various PATRRs that differ regarding their size and symmetry. At physiological ionic strength, a cruciform structure is most frequently observed for the symmetric PATRR22, less often for the symmetric PATRR11, but not for the other PATRRs. In wild-type E. coli, only these two PATRRs undergo extensive instability, consistent with the relatively high incidence of the t(11;22) in humans. The resultant deletions are putatively mediated by central cleavage by the structure-specific endonuclease SbcCD, indicating the possibility of a cruciform conformation in vivo. Insertion of a short spacer at the centre of the PATRR22 greatly reduces both its cruciform extrusion in vitro and instability in vivo. Taken together, cruciform extrusion propensity depends on the length and central symmetry of the PATRR, and is likely to determine the instability that leads to recurrent translocations in humans.