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Regulation of DIM-2-dependent repeat-induced point mutation (RIP) by the recombination-independent homologous DNA pairing in Neurospora crassa

Abstract : Repeat-induced point mutation (RIP) is a genetic process that creates cytosine-to-thymine (C-to-T) transitions in duplicated genomic sequences in fungi. RIP detects duplications irrespective of their origin, particular sequence, coding capacity, or genomic positions. Previous studies suggested that RIP involves a cardinally new mechanism of sequence recognition that operates on intact double-stranded DNAs. In the fungus Neurospora crassa, RIP can be mediated by a putative C5-cytosine methyltransferase (CMT) RID or/and a canonical CMT DIM-2. These distinct RIP pathways feature opposite substrate preferences: RID-dependent RIP is largely limited to the duplicated sequences, whereas DIM-2-dependent RIP preferentially mutates adjacent non-repetitive regions. Using DIM-2-dependent RIP as a principal readout of repeat recognition, here we show that GC-rich repeats promote stronger RIP compared to AT-rich repeats (independently of their intrinsic propensities to become mutated), with the relative contribution of AT base-pairs being close to zero. We also show that direct repeats promote much more efficient DIM-2-dependent RIP than inverted repeats; both the spacer DNA between the repeat units (the linker) and the flanking regions are similarly affected by this process. These and other results support the idea that repeat recognition for RIP involves formation of many short interspersed quadruplexes between homologous double-stranded DNAs, which need to undergo concomitant changes in their linking number to accommodate pairing.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03261442
Contributor : Eugene Gladyshev <>
Submitted on : Tuesday, June 15, 2021 - 4:53:42 PM
Last modification on : Tuesday, July 13, 2021 - 3:15:04 AM

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2021.04.05.438447v1.full.pdf
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Florian Carlier, Tinh-Suong Nguyen, Alexey Mazur, Eugene Gladyshev. Regulation of DIM-2-dependent repeat-induced point mutation (RIP) by the recombination-independent homologous DNA pairing in Neurospora crassa. 2021. ⟨pasteur-03261442⟩

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