Unpairing and gating: sequence-independent substrate recognition by FEN superfamily nucleases.

Unpairing and gating: sequence-independent substrate recognition by FEN superfamily nucleases.
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DOI:
10.1016/j.tibs.2011.10.003
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发表时间:
2012-02
影响因子:
13.8
通讯作者:
Tainer, John A.
Tainer, John A.
中科院分区:
生物学1区
文献类型:
--
作者:
Grasby, Jane A.;Finger, L. David;Tsutakawa, Susan E.;Atack, John M.;Tainer, John A.

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结构特异的5‘-核酸酶,以FENS为代表,是一个进化保守的磷酸二酯酶超家族,催化各种不同的DNA和RNA底物的精确切割。超家族成员包括Fens、EXO1、XPG、Gen1和XRN,它们在DNA复制、DNA修复、重组、转录、RNA周转和RNA干扰等许多细胞过程中发挥着关键作用。在这篇综述中,我们讨论了最近的结果,显示了保守的结构和5‘-核酸酶超家族成员的活性位点。尽管底物多样性,但这一分析表明了一种共同的、独立于序列的底物识别和切割的统一机制。新出现的超家族特征是一种令人惊讶的门控机制,需要底物的双核苷酸去配对才能访问活性位点。
Structure-specific 5′-nucleases, exemplified by the flap endonucleases (FENs), are a superfamily of evolutionarily conserved phosphodiesterases that catalyze the precise incision of a diverse range of DNA and RNA substrates. Superfamily members, that include FENs, EXO1, XPG, GEN1 and the XRNs, play key roles in many cellular processes such as DNA replication, DNA repair, recombination, transcription, RNA turnover and RNA interference. In this review we discuss recent results that show conserved architectures and active sites for members of the 5′-nuclease superfamily. Despite substrate diversity, this analysis suggests a common unified mechanism for sequence-independent substrate recognition and incision. The emerging superfamily hallmark is a surprising gating mechanism whereby double nucleotide unpairing of substrates is required to access the active site.
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