In Silico-Based Structural Evaluation to Categorize the Pathogenicity of Mutations Identified in the RAD Class of Proteins.
Journal
ACS omega
ISSN: 2470-1343
Titre abrégé: ACS Omega
Pays: United States
ID NLM: 101691658
Informations de publication
Date de publication:
21 Mar 2023
21 Mar 2023
Historique:
received:
07
12
2022
accepted:
10
02
2023
entrez:
27
3
2023
pubmed:
28
3
2023
medline:
28
3
2023
Statut:
epublish
Résumé
RAD genes, known as double-strand break repair proteins, play a major role in maintaining the genomic integrity of a cell by carrying out essential DNA repair functions via double-strand break repair pathways. Mutations in the RAD class of proteins show high susceptibility to breast and ovarian cancers; however, adequate research on the mutations identified in these genes has not been extensively reported for their deleterious effects. Changes in the folding pattern of RAD proteins play an important role in protein-protein interactions and also functions. Missense mutations identified from four cancer databases, cBioPortal, COSMIC, ClinVar, and gnomAD, cause aberrant conformations, which may lead to faulty DNA repair mechanisms. It is therefore necessary to evaluate the effects of pathogenic mutations of RAD proteins and their subsequent role in breast and ovarian cancers. In this study, we have used eight computational prediction servers to analyze pathogenic mutations and understand their effects on the protein structure and function. A total of 5122 missense mutations were identified from four different cancer databases, of which 1165 were predicted to be pathogenic using at least five pathogenicity prediction servers. These mutations were characterized as high-risk mutations based on their location in the conserved domains and subsequently subjected to structural stability characterization. The mutations included in the present study were selected from clinically relevant mutants in breast cancer pedigrees. Comparative folding patterns and intra-atomic interaction results showed alterations in the structural behavior of RAD proteins, specifically RAD51C triggered by mutations G125V and L138F and RAD51D triggered by mutations S207L and E233G.
Identifiants
pubmed: 36969410
doi: 10.1021/acsomega.2c07802
pmc: PMC10034773
doi:
Types de publication
Journal Article
Langues
eng
Pagination
10266-10277Informations de copyright
© 2023 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Nucleic Acids Res. 2006 Mar 06;34(5):1317-25
pubmed: 16522644
Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
pubmed: 12824425
J Pathol. 2015 Jan;235(1):136-46
pubmed: 25270124
Breast Cancer Res. 1999;1(1):14-7
pubmed: 11250676
BMC Bioinformatics. 2010 Nov 08;11:548
pubmed: 21059217
Mol Cell. 1998 May;1(6):783-93
pubmed: 9660962
Int J Cancer. 2006 Jun 1;118(11):2911-6
pubmed: 16385572
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
J Biol Chem. 2012 Jan 27;287(5):3366-80
pubmed: 22167183
J Hum Genet. 2000;45(3):133-7
pubmed: 10807537
Acta Med Okayama. 2005 Feb;59(1):1-9
pubmed: 15902993
Cancer Res. 2017 Aug 15;77(16):4517-4529
pubmed: 28646019
J Comput Chem. 2005 Dec;26(16):1701-18
pubmed: 16211538
Science. 1993 Mar 26;259(5103):1896-9
pubmed: 8456314
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W384-8
pubmed: 23737448
J Cell Biochem. 2018 Jan;119(1):918-925
pubmed: 28681927
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W526-31
pubmed: 15215442
PLoS One. 2011;6(9):e25632
pubmed: 21980511
Methods Biochem Anal. 2003;44:509-23
pubmed: 12647402
Hum Mutat. 2011 Apr;32(4):358-68
pubmed: 21412949
Front Genet. 2020 Nov 06;11:552971
pubmed: 33240314
Genes (Basel). 2022 Apr 11;13(4):
pubmed: 35456478
Trends Genet. 2003 Sep;19(9):505-13
pubmed: 12957544
J Biol Chem. 2000 Jun 2;275(22):16443-9
pubmed: 10749867
BMC Med Genomics. 2018 Mar 27;11(1):35
pubmed: 29580235
J Cell Biol. 2009 May 18;185(4):587-600
pubmed: 19451272
Pac Symp Biocomput. 2006;:439-50
pubmed: 17094259
BMC Med Genet. 2015 May 13;16:34
pubmed: 25967940
Genetics. 1996 Feb;142(2):383-91
pubmed: 8852838
Int J Mol Epidemiol Genet. 2013 Jun 25;4(2):77-85
pubmed: 23875061
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
Bioinformatics. 2015 Aug 15;31(16):2745-7
pubmed: 25851949
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
FEBS Lett. 2010 Sep 10;584(17):3682-95
pubmed: 20655309
Bioinformatics. 2014 Oct 15;30(20):2981-2
pubmed: 24996895
Mutat Res. 2014 Apr;762:47-54
pubmed: 24631219
NPJ Breast Cancer. 2021 Nov 15;7(1):143
pubmed: 34782604
Hum Mutat. 2012 Jan;33(1):95-9
pubmed: 21990120
Breast Cancer Res Treat. 2021 Feb;185(3):869-877
pubmed: 33452952
Int J Cancer. 2004 Jul 20;110(6):845-9
pubmed: 15170666
Nucleic Acids Res. 2019 Jan 8;47(D1):D351-D360
pubmed: 30398656
Br J Cancer. 2004 Jul 19;91(2):355-8
pubmed: 15188009
Amino Acids. 2012 Aug;43(2):603-15
pubmed: 21989830
Methods Enzymol. 1997;277:396-404
pubmed: 9379925
Bioessays. 2016 Sep;38(9):903-16
pubmed: 27492088
J Community Genet. 2017 Apr;8(2):87-95
pubmed: 28050887
Nucleic Acids Res. 2004 May 11;32(8):2556-65
pubmed: 15141025
Hum Mol Genet. 2012 Jul 1;21(13):2889-98
pubmed: 22451500
Nature. 1995 Dec 21-28;378(6559):789-92
pubmed: 8524414
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D115-9
pubmed: 14681372
Nat Genet. 2010 May;42(5):410-4
pubmed: 20400964
Hum Mol Genet. 2015 Apr 15;24(8):2125-37
pubmed: 25552646
ScientificWorldJournal. 2019 Mar 20;2019:5198931
pubmed: 31015822
Phys Chem Chem Phys. 2018 Mar 28;20(13):8676-8684
pubmed: 29537020
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W529-33
pubmed: 20478830
Biopolymers. 2008 May;89(5):380-91
pubmed: 18275088
Int J Mol Sci. 2021 Jul 16;22(14):
pubmed: 34299222
Mol Cell Biol. 1996 Sep;16(9):4832-41
pubmed: 8756642
Cancer Res. 2005 Mar 15;65(6):2089-96
pubmed: 15781618
Proteins. 2008 Apr;71(1):261-77
pubmed: 17932912
Clinics (Sao Paulo). 2021 Jan 22;76:e2052
pubmed: 33503178
Breast Cancer Res. 2011 Feb 28;13(1):R20
pubmed: 21356067
Breast Cancer Res. 2013 Dec 20;15(6):R120
pubmed: 24359560
J Biol Chem. 2000 Sep 15;275(37):29100-6
pubmed: 10871607
Br J Cancer. 2012 Apr 10;106(8):1460-3
pubmed: 22415235
J Biomol Struct Dyn. 2021 Sep;39(14):5235-5247
pubmed: 32619131
Nat Genet. 2011 Aug 07;43(9):879-882
pubmed: 21822267
Science. 1994 Oct 7;266(5182):66-71
pubmed: 7545954
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W20-5
pubmed: 15215342
Nucleic Acids Res. 1998 Mar 1;26(5):1179-84
pubmed: 9469824
Mol Cell Biol. 1996 Dec;16(12):7133-43
pubmed: 8943369
Genes Dev. 2001 Dec 15;15(24):3296-307
pubmed: 11751635
Genome Res. 2003 Sep;13(9):2129-41
pubmed: 12952881
Bioinformatics. 2004 May 22;20(8):1322-4
pubmed: 14871869
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W306-10
pubmed: 15980478
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171