The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores
dc.contributor.author | Yang, Linlin | |
dc.contributor.author | Li, Lei | |
dc.contributor.department | Chemistry and Chemical Biology, School of Science | en_US |
dc.date.accessioned | 2018-07-27T15:00:46Z | |
dc.date.available | 2018-07-27T15:00:46Z | |
dc.date.issued | 2013-06-25 | |
dc.description.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. | en_US |
dc.eprint.version | Final published version | en_US |
dc.identifier.citation | Yang, L., & Li, L. (2013). The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores. International Journal of Molecular Sciences, 14(7), 13137–13153. https://doi.org/10.3390/ijms140713137 | en_US |
dc.identifier.issn | 1422-0067 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/16847 | |
dc.language.iso | en_US | en_US |
dc.publisher | MDPI | en_US |
dc.relation.isversionof | 10.3390/ijms140713137 | en_US |
dc.relation.journal | International Journal of Molecular Sciences | en_US |
dc.rights | Attribution 3.0 United States | |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | |
dc.source | PMC | en_US |
dc.subject | thymine dimer | en_US |
dc.subject | DNA damage | en_US |
dc.subject | DNA damage repair | en_US |
dc.subject | radical | en_US |
dc.subject | transfer pathway | en_US |
dc.title | The Enzyme-Mediated Direct Reversal of a Dithymine Photoproduct in Germinating Endospores | en_US |
dc.type | Article | en_US |