Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand.
Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand.
复制标题
通过增加的运动ATPase或负载链的长度来克服骨架不连续性对Bach1（FANCJ）解旋酶的抑制。
DOI：
10.1093/nar/gkl964
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发表时间：
2006
影响因子：
14.9
通讯作者：
Brosh, Robert M Jr
中科院分区：
文献类型：
--
作者：
Gupta, Rigu;Sharma, Sudha;Doherty, Kevin M;Sommers, Joshua A;Cantor, Sharon B;Brosh, Robert M Jr
与乳腺癌相关的BRCA1相关的c端解旋酶（BACH1）与双链断裂（DSB）修复有关。最近，BACH1 （FANCJ）与染色体不稳定性疾病范可尼贫血（FA）有遗传联系。了解BACH1在细胞DNA代谢中的作用以及BACH1功能障碍如何导致肿瘤发生，需要全面研究其在DNA修复中的催化机制和分子功能。在这项研究中，我们已经确定BACH1解旋酶与双链易位链和非易位链的接触对于其沿着磷酸糖主链跟踪和解开dsDNA的能力至关重要。BACH1解旋酶结构域变体（M299I）的运动atp酶增加，使解旋酶以更熟练的方式解开骨架修饰的DNA底物。另外，增加DNA底物5 '尾部的长度可以使BACH1克服主链的不连续，这表明BACH1的加载机制对其解除受损DNA分子的能力至关重要。
The BRCA1 associated C-terminal helicase (BACH1) associated with breast cancer has been implicated in double strand break (DSB) repair. More recently, BACH1 (FANCJ) has been genetically linked to the chromosomal instability disorder Fanconi Anemia (FA). Understanding the roles of BACH1 in cellular DNA metabolism and how BACH1 dysfunction leads to tumorigenesis requires a comprehensive investigation of its catalytic mechanism and molecular functions in DNA repair. In this study, we have determined that BACH1 helicase contacts with both the translocating and the non-translocating strands of the duplex are critical for its ability to track along the sugar phosphate backbone and unwind dsDNA. An increased motor ATPase of a BACH1 helicase domain variant (M299I) enabled the helicase to unwind the backbone-modified DNA substrate in a more proficient manner. Alternatively, increasing the length of the 5′ tail of the DNA substrate allowed BACH1 to overcome the backbone discontinuity, suggesting that BACH1 loading mechanism is critical for its ability to unwind damaged DNA molecules.