Spore photoproduct lyase

Spore photoproduct lyase
Identifiers
EC no.4.1.99.14
CAS no.37290-70-3
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Spore photoproduct lyase (radical SAM)
Identifiers
Symbol?
InterProIPR023897

Spore photoproduct lyase (EC 4.1.99.14SP lyase, SPL, SplB, SplG) is a radical SAM enzyme that repairs DNA cross linking of thymine bases caused by UV-radiation. There are several types of thymine cross linking, but SPL specifically targets 5-thyminyl-5,6-dihydrothymine, which is also called spore photoproduct (SP).[1][2] Spore photoproduct is the predominant type of thymine crosslinking in germinating endospores, which is why SPL is unique to organisms that produce endospores, such as Bacillus subtilis.[3] Other types of thymine crosslinking, such as cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), are less commonly formed in endospores. These differences in DNA crosslinking are a function of differing DNA structure. Spore genomic DNA features many DNA binding proteins called small acid soluble proteins,[4] which changes the DNA from the traditional B-form conformation to an A-from conformation.[5][6] This difference in conformation is believed to be the reason why dormant spores predominantly accumulate SP in response to UV-radiation, rather than other forms of cross linking.[1][5][6] Spores cannot repair cross-linking while dormant,[3] instead the SPs are repaired during germination to allow the vegetative cell to function normally.[7] When not repaired, spore photoproduct and other types of crosslinking can cause mutations by blocking transcription and replication past the point of the crosslinking.[3] The repair mechanism utilizing spore photoproduct lyase is one of the reasons for the resilience of certain bacterial spores.

The mechanism by which SPL functions is not yet fully understood,[8] though it is known that it catalyzes light independent repair[8] of photodimer 5-thyminyl-5,6-dihydrothymine cross linking through a series of radical reactions to give back two functional thymine rings[9][3] as shown in the figure below. SPL is part of the radical SAM enzyme family, so it is known to have conserved aspects of its structure and mechanism that allow for it to be characterized as a radical SAM enzyme.[8] Radical SAM enzymes have a conserved cysteine motif, an iron-sulfur cluster within the cysteine motif, as well as S-adenosyl-L-methionine (SAM) as a cofactor.[8] A general radical SAM mechanism involves reducing the iron-sulfur cluster within the enzyme and transferring an electron to the cofactor (SAM), which cleaves a part of the structure and forms a 5'-deoxyadenosyl radical.[8] This 5'-deoxyadenosyl radical will then remove a hydrogen atom from the substrate, forming 5'-deoxyadenosine, and producing a radical on the substrate which will rearrange to form a product.[8] Given that the full mechanism of SPL function is not fully characterized, future studies will likely focus on elucidation of this process.

Spore photoproduct lyase (reaction diagram).png

Spore photoproduct lyase is part of one of two main pathways which are used to repair cross linked 5-thyminyl-5,6-dihydrothymine caused by UV radiation: the spore-specific DNA repair system (which utilizes spore photoproduct lyase), and the general nucleotide excision repair pathway (NER).[7][8] The spore-specific DNA repair system is specific to SP, whereas the NER is able to repair other types of thymine dimers, such as CPDs and 6-4PPs.[7] Spores exhibit high UV susceptibility only when both repair pathways are compromised.[7]

References[]

  1. ^ a b Moeller, Ralf (January 2007). "UV-radiation-induced formation of DNA bipyrimidine photoproducts in Bacillus subtilis endospores and their repair during germination" (PDF). International Microbiology. 10 (10): 39–46. doi:10.2436/20.1501.01.6. PMID 17407059. S2CID 10929405.
  2. ^ Munakata, Nobuo (April 1972). "Genetically controlled removal of "spore photoproduct" from deoxyribonucleic acid of ultraviolet-irradiated Bacillus subtilis spores". Journal of Bacteriology. 111 (1): 192–8. doi:10.1128/JB.111.1.192-198.1972. PMC 251257. PMID 4204907.
  3. ^ a b c d Buis JM, Cheek J, Kalliri E, Broderick JB (September 2006). "Characterization of an active spore photoproduct lyase, a DNA repair enzyme in the radical S-adenosylmethionine superfamily". The Journal of Biological Chemistry. 281 (36): 25994–6003. doi:10.1074/jbc.M603931200. PMID 16829680.
  4. ^ Setlow, Peter (1988). "Small, acid-soluble spore proteins of Bacillus species: structure, synthesis, genetics, function, and degradation". Annual Review of Microbiology. 42: 319–338. doi:10.1146/annurev.mi.42.100188.001535. PMID 3059997.
  5. ^ a b Nicholoson, W (October 1991). "Ultraviolet irradiation of DNA complexed with alpha/beta-type small, acid-soluble proteins from spores of Bacillus or Clostridium species makes spore photoproduct but not thymine dimers". Proceedings of the National Academy of Sciences of the United States of America. 88 (19): 8288–8292. doi:10.1073/pnas.88.19.8288. PMC 52493. PMID 1924287.
  6. ^ a b Mohr, S (Jan 1991). "Binding of small acid-soluble spore proteins from Bacillus subtilis changes the conformation of DNA from B to A." Proceedings of the National Academy of Sciences of the United States of America. 88 (1): 77–81. Bibcode:1991PNAS...88...77M. doi:10.1073/pnas.88.1.77. PMC 50751. PMID 1898779.
  7. ^ a b c d Yang, Linlin; Li, Lei (2014-12-04). "Spore Photoproduct Lyase: The Known, the Controversial, and the Unknown". Journal of Biological Chemistry. 290 (7): 4003–4009. doi:10.1074/jbc.r114.573675. ISSN 0021-9258. PMC 4326811. PMID 25477522.
  8. ^ a b c d e f g Berteau, Olivier; Benjdia, Alhosna (January 2017). "DNA Repair by the Radical SAM Enzyme Spore Photoproduct Lyase: From Biochemistry to Structural Investigations". Photochemistry and Photobiology. 93 (1): 67–77. doi:10.1111/php.12702. ISSN 0031-8655. PMID 28027411.
  9. ^ Wang SC, Frey PA (March 2007). "S-adenosylmethionine as an oxidant: the radical SAM superfamily". Trends in Biochemical Sciences. 32 (3): 101–10. doi:10.1016/j.tibs.2007.01.002. PMID 17291766.Note that the SPL drawings are incorrect in this paper and the erratum

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