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@article{1394050,
author = {Růžička, Michal and Kulhánek, Petr and Radová, Lenka and Čechová, Andrea and Špačková, Naděžda and Fajkusová, Lenka and Réblová, Kamila},
article_location = {San Francisco},
article_number = {8},
doi = {http://dx.doi.org/10.1371/journal.pone.0182377},
keywords = {REPAIR PROTEIN MUTS; MISMATCH REPAIR; STRAND ASYMMETRIES; CONFORMATIONAL-CHANGES; BENDING PROPENSITY; METHYLATION; RECOGNITION; MECHANISMS; HOTSPOTS; COMPLEX},
language = {eng},
issn = {1932-6203},
journal = {Plos one},
title = {DNA mutation motifs in the genes associated with inherited diseases},
url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377},
volume = {12},
year = {2017}
}
TY - JOUR
ID - 1394050
AU - Růžička, Michal - Kulhánek, Petr - Radová, Lenka - Čechová, Andrea - Špačková, Naděžda - Fajkusová, Lenka - Réblová, Kamila
PY - 2017
TI - DNA mutation motifs in the genes associated with inherited diseases
JF - Plos one
VL - 12
IS - 8
SP - nestránkováno
EP - nestránkováno
PB - Public Library of Science
SN - 19326203
KW - REPAIR PROTEIN MUTS
KW - MISMATCH REPAIR
KW - STRAND ASYMMETRIES
KW - CONFORMATIONAL-CHANGES
KW - BENDING PROPENSITY
KW - METHYLATION
KW - RECOGNITION
KW - MECHANISMS
KW - HOTSPOTS
KW - COMPLEX
UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
L2 - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182377
N2 - Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role. To detect coldspots/hotspots unaffected by population bias, we analysed the presence of germline mutations obtained from HGMD database in the 5-nucleotide segments repeatedly occurring in genes associated with common inherited disorders, in particular, the PAH, LDLR, CFTR, F8, and F9 genes. Statistically significant sequences (mutational motifs) rarely associated with mutations (coldspots) and frequently associated with mutations (hotspots) exhibited characteristic sequence patterns, e.g. coldspots contained purine tract while hotspots showed alternating purine-pyrimidine bases, often with the presence of CpG dinucleotide. Using molecular dynamics simulations and free energy calculations, we analysed the global bending properties of two selected coldspots and two hotspots with a G/T mismatch. We observed that the coldspots were inherently more flexible than the hotspots. We assume that this property might be critical for effective mismatch repair as DNA with a mutation recognized by MutS alpha protein is noticeably bent.
ER -
RŮŽIČKA, Michal, Petr KULHÁNEK, Lenka RADOVÁ, Andrea ČECHOVÁ, Naděžda ŠPAČKOVÁ, Lenka FAJKUSOVÁ and Kamila RÉBLOVÁ. DNA mutation motifs in the genes associated with inherited diseases. \textit{Plos one}. San Francisco: Public Library of Science, 2017, vol.~12, No~8, p.~nestránkováno, 16 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0182377.
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