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Int. J. Mol. Sci. 2013, 14(7), 13137-13153; doi:10.3390/ijms140713137
Review

The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores

1
 and 1,2,*
Received: 2 May 2013; in revised form: 4 June 2013 / Accepted: 7 June 2013 / Published: 25 June 2013
(This article belongs to the Special Issue Molecular Cut and Paste)
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Abstract: Spore photoproduct lyase (SPL) repairs a special thymine dimer, 5-thyminyl-5,6-dihydrothymine, which is commonly called spore photoproduct, or SP, in germinating endospores. SP is the exclusive DNA photo-damaging product found in endospores; its generation and swift repair by SPL are responsible for the spores’ extremely high UV resistance. Early in vivo studies suggested that SPL utilizes a direct reversal strategy to repair SP in the absence of light. Recently, it has been established that SPL belongs to the radical S-adenosylmethionine (SAM) superfamily. The enzymes in this superfamily utilize a tri-cysteine CXXXCXXC motif to bind a [4Fe-4S] cluster. The cluster provides an electron to the S-adenosylmethionine (SAM) to reductively cleave its C5'-S bond, generating a reactive 5'-deoxyadenosyl (5'-dA) radical. This 5'-dA radical abstracts the proR hydrogen atom from the C6 carbon of SP to initiate the repair process; the resulting SP radical subsequently fragments to generate a putative thymine methyl radical, which accepts a back-donated H atom to yield the repaired TpT. The H atom donor is suggested to be a conserved cysteine141 in B. subtilis SPL; the resulting thiyl radical likely interacts with a neighboring tyrosine99 before oxidizing the 5'-dA to 5'-dA radical and, subsequently, regenerating SAM. These findings suggest SPL to be the first enzyme in the large radical SAM superfamily (>44,000 members) to utilize a radical transfer pathway for catalysis; its study should shed light on the mechanistic understanding of the SAM regeneration process in other members of the superfamily.
Keywords: thymine dimer; DNA damage; DNA damage repair; radical; transfer pathway thymine dimer; DNA damage; DNA damage repair; radical; transfer pathway
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Yang, L.; Li, L. The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores. Int. J. Mol. Sci. 2013, 14, 13137-13153.

AMA Style

Yang L, Li L. The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores. International Journal of Molecular Sciences. 2013; 14(7):13137-13153.

Chicago/Turabian Style

Yang, Linlin; Li, Lei. 2013. "The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores." Int. J. Mol. Sci. 14, no. 7: 13137-13153.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert