Oxygen and RNA in stress-induced mutation

Abstract

Mechanisms of mutation upregulated by stress responses have been described in several organisms from bacteria to human. These mechanisms might accelerate genetic change specifically when cells are maladapted to their environment. Stress-induced mutation mechanisms differ in their genetic requirements from mutation in growing cells, occurring by different mechanisms in different assay systems, but having in common a requirement for the induction of stress-responses. Here, we review progress in two areas relevant to stress-response-dependent mutagenic DNA break repair mechanisms in Escherichia coli. First, we review evidence that relates mutation to transcription. This connection might allow mutagenesis in transcribed regions, including those relevant to any stress being experienced, opening the possibility that mutations could be targeted to regions where mutation might be advantageous under conditions of a specific stress. We review the mechanisms by which replication initiated by transcription can lead to mutation. Second, we review recent findings that, although stress-induced mutation does not require exogenous DNA-damaging agents, it does require the presence of damaged bases in DNA. For starved E. coli, endogenous oxygen radicals cause these altered bases. We postulate that damaged bases stall the replisome, which, we suggest, is required for DNA-polymerase exchange, allowing the action of low-fidelity DNA polymerases that promote mutation.

Megabase Length Hypermutation Accompanies Human Structural Variation at 17p11.2

“…Although the spectrum of junction sequences is similar between MMEJ and MMBIR, SNV is only reported up to 14 kb from microhomology in yeast MMEJ events (Sinha et al, 2017). Therefore, we propose that the events lacking SNV and indel mutations may also occur by MMBIR or BIR, but that a converging replication fork or resolution of the recombination structure could limit the mutation tract in these cases (Correa et al, 2018;Mayle et al, 2015). The absence of long-distance SNV associated with recurrent events suggests that most do not occur by BIR, but rather by homologous reciprocal exchange (crossing over) (Shaw et al, 2002).…”

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

“…Several authors have already proposed that cellular stresses (i.e., environmental fluctuations above a physiological range) induce "adaptive mutations" (i.e., mutations that occur at a high rate) or "directed mutations" (i.e., mutations occurring at specific genomic locations) [103][104][105]. A possible underlying mechanism is that stress-directed transcriptional activation of specific loci (as part of the cellular physiological adaptation) increases the probability of mutations occurring within these loci because transcription induces mechanical stresses (e.g., formation of supercoiling) that challenge the physical integrity of transcribed DNA [12,34,[104][105][106][107]. Next, how this straightforward principle establishes a continuum between physiological and genetic adaption is described below.…”

“…Transcription-dependent chromatin relaxation and ssDNA formation increase the accessibility of transcribed DNA regions to mutational agents or so-called "transcription-associated mutations" [5,12,34,[105][106][107]129].…”

Pseudouridines of tRNA Anticodon Stem-Loop Have Unexpected Role in Mutagenesis in Pseudomonas sp.

“…Mutation rates can also vary between different chromosomal regions [ 46 , 47 , 48 , 49 ]. The frequency of mutations can be elevated either constitutively, due to loss-of function mutations in genes for DNA repair systems [ 50 ], or transiently, in response to DNA damage or other stress situations [ 51 , 52 , 53 , 54 , 55 , 56 ]. Transiently increased mutability could be a consequence of the action of specialized DNA polymerases following exposure to DNA damaging agents or other environmental stresses [ 57 , 58 ].…”