Trinucleotide repeat instability via DNA base excision repair
نویسندگان
چکیده
منابع مشابه
DNA repair and trinucleotide repeat instability.
enes harboring certain trinucleotide repeat (TNR) sequences are at risk for high-frequency mutations that expand or contract the repeat tract. The triplet sequences CNG (where N = any nucleotide) and GAA are known to cause human disease when they expand by more than a few repeats in certain key genes. One of the crucial questions in the field is the mechanism (or, more likely, mechanisms) of tr...
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Base excision repair (BER) of an oxidized base within a trinucleotide repeat (TNR) tract can lead to TNR expansions that are associated with over 40 human neurodegenerative diseases. This occurs as a result of DNA secondary structures such as hairpins formed during repair. We have previously shown that BER in a TNR hairpin loop can lead to removal of the hairpin, attenuating or preventing TNR e...
متن کاملTissue specificity in DNA repair: lessons from trinucleotide repeat instability.
DNA must constantly be repaired to maintain genome stability. Although it is clear that DNA repair reactions depend on cell type and developmental stage, we know surprisingly little about the mechanisms that underlie this tissue specificity. This is due, in part, to the lack of adequate study systems. This review discusses recent progress toward understanding the mechanism leading to varying ra...
متن کاملBase excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion
Trinucleotide repeat (TNR) expansion is responsible for numerous human neurodegenerative diseases. However, the underlying mechanisms remain unclear. Recent studies have shown that DNA base excision repair (BER) can mediate TNR expansion and deletion by removing base lesions in different locations of a TNR tract, indicating that BER can promote or prevent TNR expansion in a damage location-depe...
متن کاملCrosstalk between MSH2–MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair
Studies in knockout mice provide evidence that MSH2-MSH3 and the BER machinery promote trinucleotide repeat (TNR) expansion, yet how these two different repair pathways cause the mutation is unknown. Here we report the first molecular crosstalk mechanism, in which MSH2-MSH3 is used as a component of the BER machinery to cause expansion. On its own, pol β fails to copy TNRs during DNA synthesis,...
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ژورنال
عنوان ژورنال: DNA Repair
سال: 2020
ISSN: 1568-7864
DOI: 10.1016/j.dnarep.2020.102912