Inflammation due to necroptosis has been implicated in mediating major human inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease,

amyotrophic lateral sclerosis, Alzheimer’s disease and progressive atherosclerotic lesions

TLS Online TPP Program

#Id: 6125

#Unit 3. Fundamental Processes

Humans have the enzyme hSMUG1, which removes any U residues that occur in single-stranded DNA during replication or transcription.  Two other human DNA glycosylases, TDG and MBD4, remove either U or T residues paired with G, generated by deamination of cytosine or 5-methylcytosine, respectively.

TLS Online TPP Program

#Id: 6126

#Unit 3. Fundamental Processes

DNA glycosylases recognize and remove formamidopyrimidine and 8-hydroxyguanine (both arising from purine oxidation), hypoxanthine (arising from adenine deamination), and alkylated bases such as 3-methyladenine and 7-methylguanine.

TLS Online TPP Program

#Id: 6127

#Unit 3. Fundamental Processes

Enzymes that remove bases from DNA are called glycosylases and lyases

TLS Online TPP Program

#Id: 6128

#Unit 3. Fundamental Processes

Glycosylase action is followed by the endonuclease APE1, which cleaves the polynucleotide chain on the 5’ side. This in turn attracts a replication complex including the DNA polymerase d/E and ancillary components, which performs a short synthesis reaction extending for two to 10 nucleotides. The displaced material is removed by the endonuclease FEN1.

TLS Online TPP Program

#Id: 6129

#Unit 3. Fundamental Processes

When the initial removal involves lyase action, the endonuclease APE1 instead recruits DNA polymerase b to replace a single nucleotide. The nick is then sealed by the ligase XRCC1/ligase-3. This is called the short-patch pathway.

TLS Online TPP Program

#Id: 6130

#Unit 3. Fundamental Processes

Alkyladenine DNA glycosylase (AAG), recognizes and removes a variety of alkylated substrates, including 3-methyladenine, 7-methylguanine, and hypoxanthine.