Elucidation of spore-photoproduct formation by isotope labeling.

Elucidation of spore-photoproduct formation by isotope labeling.
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DOI:
10.1002/anie.201005228
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发表时间:
2010-12-17
影响因子:
16.6
通讯作者:
Li, Lei
Li, Lei
中科院分区:
化学1区
文献类型:
--
作者:
Lin, Gengjie;Li, Lei

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紫外光由于其相对高的能量和生物大分子的有效吸收而对大多数微生物是致命的。然而,导致炭疽和破伤风等多种人类疾病的细菌内生孢子对紫外线辐射具有极强的抵抗力。例如,一些芽孢杆菌孢子对紫外线的抗性可以是相应营养细胞的100倍。[1]极不寻常的抗紫外线是由于独特的DNA光化学加上有效的损伤修复内生孢子。[2-8]在阐明损伤修复过程方面取得了进展。[6-9]然而,尽管SP是在将近半个世纪前被发现的[10],尽管科学界对它是如何形成的有着浓厚的兴趣[2,11],但人们对孢子DNA光化学的机制知之甚少。[12]胸腺嘧啶(T)是最紫外敏感的核碱基。[12]在典型的细胞中,在光化学激发后,T残基可以与相邻的T残基二聚化以产生环丁烷嘧啶二聚体和嘧啶(6-4)光产物。相比之下,内生孢子中的主要DNA光产物是独特的胸腺嘧啶二聚体,5-胸腺嘧啶基-5,6-二氢胸腺嘧啶,也称为孢子光产物或SP。[13]孢子表达一种特异性酶,孢子光产物裂解酶(SPL),其在萌发早期有效地逆转SP-二聚体的形成,从而使孢子能够恢复其正常的生命周期(方案1)。[2、13]
UV light is lethal to most microorganisms owing to its relatively high energy and efficient absorption by biomacromolecules. However, bacterial endospores, which are responsible for a number of human diseases, such as anthrax and tetanus, are extremely resistant to UV radiation. For example, some Bacillus spores can be 100 times more resistant to UV light than the corresponding vegetative cells.[1] The highly unusual UV resistance is due to unique DNA photochemistry coupled with efficient damage repair in endospores.[2–8] Progress has been made in the elucidation of the damagerepair process.[6–9] However, although SP was discovered nearly half a century ago,[10] and despite the strong interest of the scientific community in how it is formed,[2, 11] little is known about the mechanism of spore-DNA photochemistry.[12]Thymine (T) is the most UV-sensitive nucleobase.[12] In typical cells after photochemical excitation, a T residue can dimerize with an adjacent T residue to generate cyclobutane pyrimidine dimers and pyrimidine (6–4) photoproducts. In contrast, the dominant DNA photoproduct in endospores is a unique thymine dimer, 5-thyminyl-5, 6-dihydrothymine, also called spore photoproduct or SP.[13] Spores express a specific enzyme, spore photoproduct lyase (SPL), which effectively reverses SP-dimer formation at the early germination phase and thus enables spores to resume their normal life cycle (Scheme 1).[2, 13]
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