scholarly journals Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation

Science ◽  
2016 ◽  
Vol 351 (6277) ◽  
pp. 1094-1097 ◽  
Author(s):  
S. Uphoff ◽  
N. D. Lord ◽  
B. Okumus ◽  
L. Potvin-Trottier ◽  
D. J. Sherratt ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mutation Rate ◽  
Rate Variation ◽  
Cell Mutation ◽  
Damage Response ◽  
Mutation Rate Variation

scholarly journals SETD2 alterations impair DNA damage recognition and lead to resistance to chemotherapy in leukemia

Blood ◽  
2017 ◽  
Vol 130 (24) ◽  
pp. 2631-2641 ◽  
Author(s):  
Brenton G. Mar ◽  
S. Haihua Chu ◽  
Josephine D. Kahn ◽  
Andrei V. Krivtsov ◽  
Richard Koche ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Mutation Rate ◽  
Histone 3 ◽  
Damage Recognition ◽  
Key Points ◽  
Damage Response ◽  
Dna Damage Recognition ◽  
Resistance To Chemotherapy

Key Points Alterations of SETD2, a histone 3 lysine 36 trimethyl (H3K36me3) transferase leads to resistance to DNA damaging-chemotherapy in leukemia. Low H3K36me3 levels impair DNA damage response and increase mutation rate, which may be targeted by H3K36me3 demethylase inhibition.

scholarly journals Expression of progerin does not result in an increased mutation rate

2016 ◽  
Author(s):  
Emmanuelle Deniaud ◽  
Shelagh Boyle ◽  
Wendy Bickmore
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Mutation Rate ◽  
Genetic Defect ◽  
Lamin A ◽  
Mutant Form ◽  
Premature Ageing ◽  
Damage Response ◽  
Per Se

AbstractIn the premature ageing disease Hutchinson-Gilford progeria syndrome (HGPS) the underlying genetic defect in the lamin A gene leads to accumulation at the nuclear lamina of progerin – a mutant form of lamin A that cannot be correctly processed. This has been reported to result in defects in the DNA damage response and in DNA repair, leading to the hypothesis that, as in normal ageing and in other progeroid syndromes caused by mutation of genes of the DNA repair and DNA damage response pathways, increased DNA damage may be responsible for the premature ageing phenotypes in HGPS patients. However, this hypothesis is based upon the study of markers of the DNA damage response, rather than measurement of DNA damage per se or the consequences of unrepaired DNA damage -mutation. Here, using a mutation reporter cell line, we directly compared the inherent and induced mutation rates in cells expressing wild-type lamin A or progerin. We find no evidence for an elevated mutation rate in progerin-expressing cells. We conclude that the cellular defect in HGPS cells does not lie in the repair of DNA damage per se.

scholarly journals How sequence context-dependent mutability drives mutation rate variation in the genome

2021 ◽  
Author(s):  
Madeleine Oman ◽  
Aqsa Alam ◽  
Rob Ness
Keyword(s):  
Dna Damage ◽  
Mutation Rate ◽  
Genetic Diseases ◽  
Purifying Selection ◽  
Rate Variation ◽  
Sequence Evolution ◽  
Sequence Context ◽  
Simple Process ◽  
Human Mutation ◽  
Mutation Rate Variation

The rate of mutations varies >100-fold across the genome, altering the rate of evolution, and susceptibility to genetic diseases. The strongest predictor of mutation rate is the sequence itself, varying 75-fold between trinucleotides. The fact that DNA sequence drives its own mutation rate raises a simple but important prediction; highly mutable sequences will mutate more frequently and eliminate themselves in favour of sequences with lower mutability, leading to a lower equilibrium mutation rate. However, purifying selection constrains changes in mutable sequences, causing higher rates of mutation. We conduct a simulation using real human mutation data to test if (1) DNA evolves to a low equilibrium mutation rate and (2) purifying selection causes a higher equilibrium mutation rate in the most important regions of the genome. We explore how this simple process affects sequence evolution in the genome, and discuss the implications for modelling evolution and susceptibility to DNA damage.

2118-P: Regulation of Ataxia-Telangiectasia and Rad3-Related (ATR)–Dependent DNA Damage Response by Nitric Oxide in ß-Cells

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 2118-P
Author(s):  
CHAY TENG YEO ◽  
BRYNDON OLESON ◽  
JOHN A. CORBETT ◽  
JAMIE K. SCHNUCK
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Damage Response

DNA damage response and neuroprotection

10.2741/2862 ◽  
2008 ◽  
Vol 13 (13) ◽  
pp. 2504 ◽  
Author(s):  
Inna, I. Kruman
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Damage Response
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