In silico analysis on the functional and structural impact of Rad50 mutations involved in DNA strand break repair

PeerJ
Juwairiah RemaliShazrul Fazry

Abstract

DNA double strand break repair is important to preserve the fidelity of our genetic makeup after DNA damage. Rad50 is one of the components in MRN complex important for DNA repair mechanism. Rad50 mutations can lead to microcephaly, mental retardation and growth retardation in human. However, Rad50 mutations in human and other organisms have never been gathered and heuristically compared for their deleterious effects. It is important to assess the conserved region in Rad50 and its homolog to identify vital mutations that can affect functions of the protein. In this study, Rad50 mutations were retrieved from SNPeffect 4.0 database and literature. Each of the mutations was analyzed using various bioinformatic analyses such as PredictSNP, MutPred, SNPeffect 4.0, I-Mutant and MuPro to identify its impact on molecular mechanism, biological function and protein stability, respectively. We identified 103 mostly occurred mutations in the Rad50 protein domains and motifs, which only 42 mutations were classified as most deleterious. These mutations are mainly situated at the specific motifs such as Walker A, Q-loop, Walker B, D-loop and signature motif of the Rad50 protein. Some of these mutations were predicted to negatively affect seve...Continue Reading

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Citations

May 14, 2021·Nature Communications·Florian Roisné-HamelinStéphane Marcand
Oct 5, 2021·Nucleic Acids Research·Kannan HariniM Michael Gromiha

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Datasets Mentioned

BETA
AAB07119.1

Methods Mentioned

BETA
glycosylation

Software Mentioned

Clustal Omega
BLASTP
MUpro
PredictSNP
Mutant
SwissVar
SIFT
InterPro
Mu
SNPeffect

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