A bacterial DNA repair pathway specific to a natural antibiotic.
A bacterial DNA repair pathway specific to a natural antibiotic.
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DOI：
10.1111/mmi.14158
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发表时间：
2019-03
影响因子：
3.6
通讯作者：
Simmons LA
中科院分区：
文献类型：
--
作者：
Burby PE;Simmons LA
所有生物体都具有DNA修复途径，用于维持其遗传物质的完整性。虽然许多DNA修复途径已经被很好地理解，但新的途径仍在不断被发现。在这里，我们报告了枯草芽孢杆菌中抗生素特异性DNA修复途径，该途径由以前未被表征的解旋酶（mrfA）和核酸外切酶（mrfB）组成。mrfA和mrfB的缺失导致对DNA损伤剂丝裂霉素C的敏感性，但对任何其他类型的DNA损伤测试没有敏感性。我们发现MrfAB的功能独立于典型核苷酸切除修复，形成了一种新的切除修复途径。我们证明MrfB是一种金属依赖的外切酶，并且MrfB的n端是与MrfA相互作用所必需的。我们确定MrfAB在体内不能解除链间交联，这表明MrfAB对单加合物或链内交联具有特异性。系统发育分析揭示了MrfAB在不同细菌门中的同源性，交叉互补表明MrfAB的功能在密切相关的物种中是保守的。枯草芽孢杆菌是一种土壤生物，丝裂霉素C是一种由土壤细菌薰衣草链霉菌产生的天然抗生素。MrfAB的特异性表明，这些蛋白是对有丝裂霉素产生细菌的环境的适应。细菌拥有DNA修复途径来维持其遗传物质的完整性。推测的解旋酶MrfA和核酸外切酶MrfB是枯草芽孢杆菌丝裂霉素C （MMC）特异性DNA修复途径的一部分。尽管存在于许多细菌物种中，MrfAB修复MMC损伤DNA的活性似乎仅限于密切相关的物种，这表明尽管序列保守，这些蛋白质已经进化到每种细菌的特定修复需求。
All organisms possess DNA repair pathways that are used to maintain the integrity of their genetic material. Although many DNA repair pathways are well understood, new pathways continue to be discovered. Here, we report an antibiotic specific DNA repair pathway in Bacillus subtilis that is composed of a previously uncharacterized helicase (mrfA) and exonuclease (mrfB). Deletion of mrfA and mrfB results in sensitivity to the DNA damaging agent mitomycin C, but not to any other type of DNA damage tested. We show that MrfAB function independent of canonical nucleotide excision repair, forming a novel excision repair pathway. We demonstrate that MrfB is a metal-dependent exonuclease and that the N-terminus of MrfB is required for interaction with MrfA. We determined that MrfAB failed to unhook inter-strand crosslinks in vivo, suggesting that MrfAB are specific to the monoadduct or the intra-strand crosslink. A phylogenetic analysis uncovered MrfAB homologs in diverse bacterial phyla, and cross-complementation indicates that MrfAB function is conserved in closely related species. B. subtilis is a soil dwelling organism and mitomycin C is a natural antibiotic produced by the soil bacterium Streptomyces lavendulae. The specificity of MrfAB suggests that these proteins are an adaptation to environments with mitomycin producing bacteria. Abbreviated Summary Bacteria possess DNA repair pathways to maintain the integrity of their genetic material. The putative helicase MrfA and the exonuclease MrfB are part of a mitomycin C (MMC) specific DNA repair pathway in Bacillus subtilis. Despite being present in many bacterial species, MrfAB activity in repairing MMC damaged DNA appears to be restricted to closely related species, suggesting that despite sequence conservation these proteins have evolved to the specific repair needs of each bacterium.
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影响因子：
4.5
作者：
Burby PE;Simmons ZW;Schroeder JW;Simmons LA
通讯作者：
Simmons LA
影响因子：
3.2
作者：
Ivancic-Bace, Ivana;Vlasic, Ignacija;Brcic-Kostic, Krunoslav
通讯作者：
Brcic-Kostic, Krunoslav
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
2.9
作者：
KUMAR, S;LIPMAN, R;TOMASZ, M
通讯作者：
TOMASZ, M
影响因子：
8.8
作者：
Bochman ML;Paeschke K;Chan A;Zakian VA
通讯作者：
Zakian VA