Glycosylases

Removes uracil, thymine or ethenocytosine opposite guanine 

Removes oxidized and ring-opened purines including 8-oxoG and formamidopyrimidine 

Removes 3-methylpurines, 7-methylpurines, 3-and 7-ethylpurines, ethenoadenine and 02-methylpyrimidines 

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Chemistry of glycosylases and endonucleases involved in base-excision repair 98CRV1221. 

Base excision- repair Spontaneous, chemical, or radiation damage to a single base Base removal byN-glycosylase, abasic sugar removal, replacement... 

Figure 36-23. Base excision-repair of DNA. The enzyme uracil DNA glycosylase removes the uracil created by spontaneous deamination of cytosine in the DNA. An endonuclease cuts the backbone near the defect then, after an endonuclease removes a few bases, the defect is filled in by the action of a repair polymerase and the strand is rejoined by a ligase. (Courtesy of B Alberts.)...

The great potential of QM/MM calculations has attracted much attention in the past decade and the number of studies published in recent years is now so large that it is not possible to cover them all here. Among recent QM/MM applications at different levels are para-hydroxybenzoate hydrolase [56, 74], citrate synthase [4-6, 52], uracil-DNA glycosylase [88], neuraminidase [89, 90], aldose reductase [91], human thrombin [92], glutathione S-transferases [57], and HIV protease [93]. 

Mismatch Repair. Mispairs that break the normal base-pairing rules can arise spontaneously due to DNA biosynthetic errors, events associated with genetic recombination and the deamination of methylated cytosine (Modrich, 1987). With the latter, when cytosine deaminates to uracil, an endonuclease enzyme, /V-uracil-DNA glycosylase (Lindahl, 1979), excises the uracil residue before it can pair with adenine at the next replication. However, 5-methyl cytosine deaminates to form thymine and will not be excised by a glycosylase. As a result, thymine exits on one strand paired with guanine on the sister strand, that is, a mismatch. This will result in a spontaneous point mutation if left unrepaired. For this reason, methylated cytosines form spontaneous mutation hot-spots (Miller, 1985). The cell is able to repair mismatches by being able to distinguish between the DNA strand that exists before replication and a newly synthesized strand. 

L4. Longo, M. C., Beminger, M. S., and Hartley, J. L., Use of uracil DNA glycosylase to control carry-over contamination in polymerase chain reactions. Gene 93, 125-128 (1990). 

Bhakat KK, Hazra TK, Mitra S (2004) Acetylation of the human DNA glycosylase NE1L2 and inhibition of its activity. Nucleic Acids Research 32(10) 3033-3039... 

Cytosine deamination (G ) Spontaneous/ chemicals Uracil glycosylase AP endonuclease DNA polymerase DNA ligase... 

A uracil glycosylase recognizes and removes the uracil base, leaving an apyrimidinic (AP) site in the DNA strand. 

MBD4 Contains MBD domain and a repair domain (T-G mismatch glycosylase) Thymine glycosylase that binds to the product of deamination at methylated CpG sites Co-localizes with heavily methylated satellite DNA in mouse cells expressed in somatic tissues and in ES cells... 

MBD4 is the only family member with a different function in addition to the MBD motif it has a glycosylase domain and is mainly involved in DNA repair removing the thymidine from the TdG, resulting from the spontaneous deamination of 5mC (see Section 2.4) [93]. 

While the Uterature is rich in scientific information on glucosylases, recent interest has focused on the hypothesis that all these enzymes share a common catal3iic mechanism, despite differences in their product specificity (57). Indeed, it has been proposed that all glycosylases share the same basic chemical mechanism (58). Tlie a-amylases have been the focus of much of this attention, as the primary protein sequence (59), tertiary protein structure (54,55) and catalytic mechanism (57) have been recently delineated. 

METHYLADENINE-DNA GLYCOSYLASE 3-METHYLADENINE-DNA GLYCOSYLASE N-Methyl-L-alanine,... 

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