Thymine 5-methyl cytosine

Pyrimidine nucleosides of cytosine, uracil, thymine, methyl cytosine are obtained as products of nucleic acid hydrolysis. Vicine, a D-glucoside of 2, 5-diamino-4, 6-dihydroxy pyrimidine occurs in plants. 

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. 

Some time ago, an allyl-like radical was observed in irradiated crystals of 5 -dCMP [26]. This radical was thought to be a sugar radical, although no likely scheme was proposed for its formation. It now appears that this radical is formed on 5-methyl cytosine impurities in these crystals [27]. This radical forms by deprotonation at the methyl group of the cytosine cation, 5meCyt(Me—H) , and may have important consequences in the radiation chemistry of DNA since the ionization potential of 5-methyl cytosine is lower than that of either cytosine or thymine. 

CG doublets. The only modified base commonly found in eukaryotes is 5-methylcytosine,222/223 which upon deamination becomes thymine (Eq. 27-1). Most methylation occurs when C is followed by G. Usually 60-90% of all 5 -CG sequences (CpG sequences) in eukaryotic DNA are methylated. However, the fraction of methylated cytosine varies from almost zero for Drosophilia, Caenorhabditis, and Saccharomyces to as much as 30% in higher plants.224... 

Please view the following deamination example, Deaminated 5-methyl-cytosine is identical to thymine, Hence, the overall scenario of deamination of 5-methyl-cyto-sine followed by replication involves the conversion of 5-methyl-C G to T A,... 

Deamination of 5-methyl-cytosine results in the formation of a T C mispair. This mispair is sloivly repaired by a special enzyme, which slowly hydrolyzes the resiciue of T. The enzyme is called thymine DNA glycosytase (Neddennann and jirieny, 1993)-... 

The photophysical behaviour of a series of methylated angelicins has been recorded using flash photochemical techniques. Irradiation of the complex formed between 4,6-dimethyltetrahydrobenzoangelicin and DNA results in the formation of cycloadducts. These arise by addition between the pyrimidine bases, thymine and cytosine and the furan ring of the angelicin. 

FIGURE 2. Ion-exclusion chromatography of (a) known purines and pyrimidines (b) purines and pyrimidines extracted from the B, . horizon of a Spodosol. HX = uracil U = unknown T = thymine G = guanine A = adenine C = cytosine MC = 5 methyl cytosine (Cortez and Schnitzer, 1979b). 

N2O3 formed by a third order reaction, can deaminate DNA bases yielding uracil from cytosine, xanthine from guanine, methyl cytosine from thymine and hypoxanthine from adenine [ 56 ]. Furthermore, it can react with secondary amines to yield carcinogenic N-nitrosoamines, which can damage DNA by alkylation, [57]. 

FIGURE 23-25 Formation of a spontaneous point mutation by deamination of 5-methyl cytosine (C) to form thymine (T). If the resulting T-G base pair is not restored to the normai C-G base pair by base excision-repair mechanisms (D), it will lead to a permanent change in sequence following DNA replication (i.e., a mutation) (B). After one round of replication, one daughter DNA molecule will have the mutant T-A base pair and the other will have the wild-type C-G base pair. 

Many spontaneous mutations are point mutations, which involve a change in a single base pair in the DNA sequence. One of the most frequent point mutations comes from deamination of a cytosine (C) base, which converts it into a uracil (U) base. In addition, the common modified base 5-methyl cytosine forms thymine when it is deaminated. If these alterations are not corrected before the DNA is replicated, the cell will use the strand containing U or T as template to form a U-A or T-A base pair, thus creating a permanent change to the DNA sequence (Figure 23-25). 

The bases found in DNA are either purines (adenine or guanine) or pyrimidines (cytosine or thymine), although some modified bases are found, such as 5 methyl cytosine. Ribonucleic acid contains adenine, cytosine, and guanine as in DNA, but thymine is usually replaced by uracil, which lacks the 5-methyl group present in thymine (Fig. 2.2). In some types of RNA, unlike DNA, modified bases are common. In both DNA and RNA the base is attached through a nitrogen to the... 

Transient Decay and Spectra Thymine, Uracil, and 5-Methyl-cytosine. Typical oscillograms showing decay of transient absorption in N20 saturated 5 X 10"4M s iKBHI1 Figure 1. With... 

Figure 6. Absorption spectra of transient species formed on irradiation of N20 saturated 5 X 10 M solutions of pyrimidine bases. The optical density is the maximum observed during formation and decay of the transient. Doses were 800 rads/pulse for thymine (A and B) and 5-methyl-cytosine (C), and 1070 rads/pulse for uracil (C and D)...

It is used to maximize the maintenance of the integrity of the information encoded by DNA. Cytosine can spontaneously deaminate to form uracil this damage is repaired by base excision repair. If uracil rather than thymine were used in DNA, then correctly positioned uracil would be indistinguishable from that arising from cytosine deamination. Use of thymine (methylated uracil) in DNA avoids this problem. 

In addition to the five bases named adenine, guanine, cytosine, uracil, and thymine (3-methyl uracil), the polynucleotides also contain small amounts of their derivatives. Up to 6% of 5-methyl cytosine occurs in vegetable DNA and up to 1.5% of this occurs in certain mammalian DNA. In addition, 1-methyl guanine or dihydrouracil is found in RNA. These derivatives are produced in RNA by modification of the bases after the in vitro RNA synthesis. 

According to the Chargaff rule, each nucleic acid has as much adenine as thymine (Table 29-4). There are also equal amounts of guanine and cytosine or 5-methyl cytosine. Because of this, the term base pairing of A/T, G/C, G/5MC, and A/ U is used. The rule applies well to DNA, but there are often significant deviations in the case of RNA. This difference is closely related to the differences in physical structure between DNA and RNA (see also Section 29.4). 

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