While human cells utilize both short- and long-patch BER, the yeast Saccharomyces cerevisiae was long thought to lack a short-patch pathway because it does not have homologs of several mammalian short-patch proteins, including pol β, DNA ligase III, XRCC1, and the kinase domain of PNKP. Pathway preference may differ between organisms, as well. Some lesions, such as oxidized or reduced AP sites, are resistant to pol β lyase activity and, therefore, must be processed by long-patch BER. Various factors are thought to influence this decision, including the type of lesion, the cell cycle stage, and whether the cell is terminally differentiated or actively dividing. The choice between short- and long-patch repair is currently under investigation. The choice between long-patch and short-patch repair In addition to base lesions, the downstream steps of BER are also utilized to repair single-strand breaks. Uracil inappropriately incorporated in DNA or formed by deamination of cytosine.( Thymidine products following deamination of 5-methylcytosine are more difficult to recognize, but can be repaired by mismatch-specific glycosylases) Xanthine formed from deamination of guanine. Deaminated bases: hypoxanthine formed from deamination of adenine.Alkylated bases: 3-methyladenine, 7-methylguanosine.Oxidized bases: 8-oxoguanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG, FapyA).Other examples of base lesions repaired by BER include:
For example, incorporation of adenine across from 8-oxoguanine (right) during DNA replication causes a G:C base pair to be mutated to T:A. These modifications can affect the ability of the base to hydrogen-bond, resulting in incorrect base-pairing, and, as a consequence, mutations in the DNA. Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, and alkylation. 8-oxoguanine forms a Hoogsteen base pair with adenine
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