Repeat-induced point mutation is a genetic process that creates cytosine-to-thymine (C-to-T) transitions in duplicated genomic sequences in fungi. Repeat-induced point mutation detects duplications (irrespective of their origin, specific sequence, coding capacity, and genomic positions) by a recombination-independent mechanism that likely matches intact DNA double helices directly, without relying on the annealing of complementary single strands. In the fungus Neurospora crassa, closely positioned repeats can induce mutation of the adjoining nonrepetitive regions. This process is related to heterochromatin assembly and requires the cytosine methyltransferase DIM-2. Using DIM-2-dependent mutation as a readout of homologous pairing, we find that GC-rich repeats produce a much stronger response than AT-rich repeats, independently of their intrinsic propensity to become mutated. We also report that direct repeats trigger much stronger DIM-2-dependent mutation than inverted repeats. These results can be rationalized in the light of a recently proposed model of homologous DNA pairing, in which DNA double helices associate by forming sequence-specific quadruplex-based contacts with a concomitant release of supercoiling. A similar process featuring pairing-induced supercoiling may initiate epigenetic silencing of repetitive DNA in other organisms, including humans.

重复诱导的点突变是一种遗传过程，它在真菌的重复基因组序列中产生胞嘧啶到胸腺嘧啶 (C-to-T) 的转变。重复诱导的点突变通过可能直接匹配完整 DNA 双螺旋的重组独立机制检测重复（无论其来源、特定序列、编码能力和基因组位置如何），而不依赖于互补单链的退火。在真菌粗糙脉孢菌中，紧密定位的重复可以诱导相邻非重复区域的突变。该过程与异染色质组装有关，需要胞嘧啶甲基转移酶 DIM-2。使用依赖于 DIM-2 的突变作为同源配对的读数，我们发现富含 GC 的重复比富含 AT 的重复产生更强的反应，与其内在的突变倾向无关。我们还报告说，直接重复比反向重复触发更强的 DIM-2 依赖性突变。根据最近提出的同源 DNA 配对模型，可以使这些结果合理化，其中 DNA 双螺旋通过形成序列特异性的基于四链体的接触与伴随的超螺旋释放而结合。