Structural parameters of palindromic repeats determine the specificity of nuclease attack of secondary structures.
Structural parameters of palindromic repeats determine the specificity of nuclease attack of secondary structures.
复制标题
DOI：
10.1093/nar/gkab168
复制
发表时间：
2021-04-19
影响因子：
14.9
通讯作者：
Lobachev KS
中科院分区：
文献类型：
--
作者：
Ait Saada A;Costa AB;Sheng Z;Guo W;Haber JE;Lobachev KS
回文序列是许多生物体中染色体不稳定的重要来源，并且与人类疾病的发病机制有关。在这项研究中，我们研究了哪些核酸酶负责酿酒酵母中发夹和十字形结构的切割以及反向重复序列处双链断裂的产生。我们证明，结构特异性核酸酶与回文脆性的关系取决于反向重复序列之间的距离及其转录状态。 Mre11 复合体的攻击仅限于环少于 9 个核苷酸的发夹。 RPA 耗尽后，这种限制得到缓解，表明 RPA 控制二级结构的稳定性和/或形成，否则会导致复制叉停滞和 DSB 形成。十字形的 Mus81-Mms4 切割发生在不同但不聚合的转录或非转录重复序列处。我们的研究还揭示了完美和准回文脆性的第三条途径，其中涉及细胞周期 G2 阶段的十字形解析。
Palindromic sequences are a potent source of chromosomal instability in many organisms and are implicated in the pathogenesis of human diseases. In this study, we investigate which nucleases are responsible for cleavage of the hairpin and cruciform structures and generation of double-strand breaks at inverted repeats in Saccharomyces cerevisiae. We demonstrate that the involvement of structure-specific nucleases in palindrome fragility depends on the distance between inverted repeats and their transcriptional status. The attack by the Mre11 complex is constrained to hairpins with loops <9 nucleotides. This restriction is alleviated upon RPA depletion, indicating that RPA controls the stability and/or formation of secondary structures otherwise responsible for replication fork stalling and DSB formation. Mus81-Mms4 cleavage of cruciforms occurs at divergently but not convergently transcribed or nontranscribed repeats. Our study also reveals the third pathway for fragility at perfect and quasi-palindromes, which involves cruciform resolution during the G2 phase of the cell cycle.
登录
查看更多内容
影响因子：
4
作者：
Deng, Sarah K.;Chen, Huan;Symington, Lorraine S.
通讯作者：
Symington, Lorraine S.
影响因子：
16
作者：
Apone, LM;Virbasius, CA;Green, MR
通讯作者：
Green, MR
影响因子：
16
作者：
Eykelenboom, John K.;Blackwood, John K.;Leach, David R. F.
通讯作者：
Leach, David R. F.
影响因子：
64.8
作者：
Bishop, AC;Ubersax, JA;Shokat, KM
通讯作者：
Shokat, KM
影响因子：
16
作者：
Darmon E;Eykelenboom JK;Lincker F;Jones LH;White M;Okely E;Blackwood JK;Leach DR
通讯作者：
Leach DR