The role of DNA polymerase I in tolerating single-strand breaks generated at clustered DNA damage in Escherichia coli.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
18 Aug 2024
Historique:
received: 17 05 2024
accepted: 08 08 2024
medline: 19 8 2024
pubmed: 19 8 2024
entrez: 18 8 2024
Statut: epublish

Résumé

Clustered DNA damage, when multiple lesions are generated in close proximity, has various biological consequences, including cell death, chromosome aberrations, and mutations. It is generally perceived as a hallmark of ionizing radiation. The enhanced mutagenic potential of lesions within a cluster has been suggested to result, at least in part, from the selection of the strand with the mutagenic lesion as the preferred template strand, and that this process is relevant to the tolerance of persistent single-strand breaks generated during an attempted repair. Using a plasmid-based assay in Escherichia coli, we examined how the strand bias is affected in mutant strains deficient in different DNA polymerase I activities. Our study revealed that the strand-displacement and 5'-flap endonuclease activities are required for this process, while 3'-to-5' exonuclease activity is not. We also found the strand template that the mutagenic lesion was located on, whether lagging or leading, had no effect on this strand bias. Our results imply that an unknown pathway operates to repair/tolerate the single-strand break generated at a bi-stranded clustered damage site, and that there exist different backup pathways, depending on which DNA polymerase I activity is compromised.

Identifiants

pubmed: 39155334
doi: 10.1038/s41598-024-69823-4
pii: 10.1038/s41598-024-69823-4
doi:

Substances chimiques

DNA Polymerase I EC 2.7.7.7
Escherichia coli Proteins 0
DNA, Bacterial 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

19124

Subventions

Organisme : KAKENHI
ID : 17K20052
Organisme : KAKENHI
ID : 21K18148

Informations de copyright

© 2024. The Author(s).

Références

Ward, J. F. Complexity of damage produced by ionizing radiation. Cold Spring Harb. Symp. Quant. Biol. 65, 377–382. https://doi.org/10.1101/sqb.2000.65.377 (2000).
doi: 10.1101/sqb.2000.65.377 pubmed: 12760053
Ward, J. F. The complexity of DNA damage: Relevance to biological consequences. Int. J. Radiat. Biol. 66, 427–432 (1994).
doi: 10.1080/09553009414551401 pubmed: 7983426
Goodhead, D. T. Initial events in the cellular effects of ionizing radiations: Clustered damage in DNA. Int. J. Radiat. Biol. 65, 7–17 (1994).
doi: 10.1080/09553009414550021 pubmed: 7905912
Gulston, M., Fulford, J., Jenner, T., de Lara, C. & O’Neill, P. Clustered DNA damage induced by gamma radiation in human fibroblasts (HF19), hamster (V79–4) cells and plasmid DNA is revealed as Fpg and Nth sensitive sites. Nucleic Acids Res. 30, 3464–3472 (2002).
doi: 10.1093/nar/gkf467 pubmed: 12140332 pmcid: 137090
Sutherland, B. M., Bennett, P. V., Sidorkina, O. & Laval, J. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation. Proc. Natl. Acad. Sci. USA 97, 103–108 (2000).
doi: 10.1073/pnas.97.1.103 pubmed: 10618378 pmcid: 26623
Sutherland, B. M., Bennett, P. V., Sutherland, J. C. & Laval, J. Clustered DNA damages induced by X rays in human cells. Radiat. Res. 157, 611–616 (2002).
doi: 10.1667/0033-7587(2002)157[0611:CDDIBX]2.0.CO;2 pubmed: 12005538
Tsao, D. et al. Induction and processing of oxidative clustered DNA lesions in 56Fe-ion-irradiated human monocytes. Radiat. Res. 168, 87–97 (2007).
doi: 10.1667/RR0865.1 pubmed: 17723001
Watanabe, R., Rahmanian, S. & Nikjoo, H. Spectrum of radiation-induced clustered non-DSB damage—A Monte Carlo track structure modeling and calculations. Radiat. Res. 183, 525–540. https://doi.org/10.1667/RR13902.1 (2015).
doi: 10.1667/RR13902.1 pubmed: 25909147
Moeini, H., Mokari, M., Alamatsaz, M. H. & Taleei, R. Calculation of the initial DNA damage induced by alpha particles in comparison with protons and electrons using Geant4-DNA. Int. J. Radiat. Biol. 96, 767–778. https://doi.org/10.1080/09553002.2020.1730015 (2020).
doi: 10.1080/09553002.2020.1730015 pubmed: 32052675
Semenenko, V. A. & Stewart, R. D. A fast Monte Carlo algorithm to simulate the spectrum of DNA damages formed by ionizing radiation. Radiat. Res. 161, 451–457 (2004).
doi: 10.1667/RR3140 pubmed: 15038766
Nikjoo, H., O’Neill, P., Wilson, W. E. & Goodhead, D. T. Computational approach for determining the spectrum of DNA damage induced by ionizing radiation. Radiat. Res. 156, 577–583 (2001).
doi: 10.1667/0033-7587(2001)156[0577:CAFDTS]2.0.CO;2 pubmed: 11604075
Nakano, T. et al. Formation of clustered DNA damage in vivo upon irradiation with ionizing radiation: Visualization and analysis with atomic force microscopy. Proc. Natl. Acad. Sci. USA 119, e2119132119. https://doi.org/10.1073/pnas.2119132119 (2022).
doi: 10.1073/pnas.2119132119 pubmed: 35324325 pmcid: 9060515
Xu, X. et al. Direct observation of damage clustering in irradiated DNA with atomic force microscopy. Nucleic Acids Res. 48, e18. https://doi.org/10.1093/nar/gkz1159 (2020).
doi: 10.1093/nar/gkz1159 pubmed: 31840169
Weinfeld, M., Rasouli-Nia, A., Chaudhry, M. A. & Britten, R. A. Response of base excision repair enzymes to complex DNA lesions. Radiat. Res. 156, 584–589 (2001).
doi: 10.1667/0033-7587(2001)156[0584:ROBERE]2.0.CO;2 pubmed: 11604076
Shikazono, N., Noguchi, M., Fujii, K., Urushibara, A. & Yokoya, A. The yield, processing, and biological consequences of clustered DNA damage induced by ionizing radiation. J. Radiat. Res. 50, 27–36 (2009).
doi: 10.1269/jrr.08086 pubmed: 19218779
Eccles, L. J., O’Neill, P. & Lomax, M. E. Delayed repair of radiation induced clustered DNA damage: Friend or foe?. Mutat. Res. 711, 134–141. https://doi.org/10.1016/j.mrfmmm.2010.11.003 (2011).
doi: 10.1016/j.mrfmmm.2010.11.003 pubmed: 21130102 pmcid: 3112496
Sage, E. & Harrison, L. Clustered DNA lesion repair in eukaryotes: Relevance to mutagenesis and cell survival. Mutat. Res. 711, 123–133. https://doi.org/10.1016/j.mrfmmm.2010.12.010 (2011).
doi: 10.1016/j.mrfmmm.2010.12.010 pubmed: 21185841
Sage, E. & Shikazono, N. Radiation-induced clustered DNA lesions: Repair and mutagenesis. Free Radic. Biol. Med. 107, 125–135. https://doi.org/10.1016/j.freeradbiomed.2016.12.008 (2017).
doi: 10.1016/j.freeradbiomed.2016.12.008 pubmed: 27939934
Malyarchuk, S., Brame, K. L., Youngblood, R., Shi, R. & Harrison, L. Two clustered 8-oxo-7,8-dihydroguanine (8-oxodG) lesions increase the point mutation frequency of 8-oxodG, but do not result in double strand breaks or deletions in Escherichia coli. Nucleic Acids Res. 32, 5721–5731 (2004).
doi: 10.1093/nar/gkh911 pubmed: 15509868 pmcid: 528796
Shikazono, N., Pearson, C., O’Neill, P. & Thacker, J. The roles of specific glycosylases in determining the mutagenic consequences of clustered DNA base damage. Nucleic Acids Res. 34, 3722–3730. https://doi.org/10.1093/nar/gkl503 (2006).
doi: 10.1093/nar/gkl503 pubmed: 16893955 pmcid: 1557791
Shikazono, N. et al. Significance of DNA polymerase I in in vivo processing of clustered DNA damage. Mutat. Res. 749, 9–15. https://doi.org/10.1016/j.mrfmmm.2013.07.010 (2013).
doi: 10.1016/j.mrfmmm.2013.07.010 pubmed: 23958410
Bellon, S., Shikazono, N., Cunniffe, S., Lomax, M. E. & O’Neill, P. Processing of thymine glycol in a clustered DNA damage site: Mutagenic or cytotoxic. Nucleic Acids Res. https://doi.org/10.1093/nar/gkp422 (2009).
doi: 10.1093/nar/gkp422 pubmed: 19468043 pmcid: 2715253
Cunniffe, S., Walker, A., Stabler, R., O’Neill, P. & Lomax, M. E. Increased mutability and decreased repairability of a three-lesion clustered DNA-damaged site comprised of an AP site and bi-stranded 8-oxoG lesions. Int. J. Radiat. Biol. 90, 468–479. https://doi.org/10.3109/09553002.2014.899449 (2014).
doi: 10.3109/09553002.2014.899449 pubmed: 24597750 pmcid: 4059193
Pearson, C. G., Shikazono, N., Thacker, J. & O’Neill, P. Enhanced mutagenic potential of 8-oxo-7,8-dihydroguanine when present within a clustered DNA damage site. Nucleic Acids Res. 32, 263–270 (2004).
doi: 10.1093/nar/gkh150 pubmed: 14715924 pmcid: 373263
Kozmin, S. G., Eot-Houllier, G., Reynaud-Angelin, A., Gasparutto, D. & Sage, E. Dissecting highly mutagenic processing of complex clustered DNA damage in yeast Saccharomyces cerevisiae. Cells https://doi.org/10.3390/cells10092309 (2021).
doi: 10.3390/cells10092309 pubmed: 34571958 pmcid: 8471780
Noguchi, M., Urushibara, A., Yokoya, A., O’Neill, P. & Shikazono, N. The mutagenic potential of 8-oxoG/single strand break-containing clusters depends on their relative positions. Mutat. Res. 732, 34–42. https://doi.org/10.1016/j.mrfmmm.2011.12.009 (2012).
doi: 10.1016/j.mrfmmm.2011.12.009 pubmed: 22261346
Sedletska, Y., Radicella, J. P. & Sage, E. Replication fork collapse is a major cause of the high mutation frequency at three-base lesion clusters. Nucleic Acids Res. 41, 9339–9348. https://doi.org/10.1093/nar/gkt731 (2013).
doi: 10.1093/nar/gkt731 pubmed: 23945941 pmcid: 3814351
Takahashi, M., Akamatsu, K. & Shikazono, N. A polymerization-based method to construct a plasmid containing clustered DNA damage and a mismatch. Anal. Biochem. 510, 129–135. https://doi.org/10.1016/j.ab.2016.07.007 (2016).
doi: 10.1016/j.ab.2016.07.007 pubmed: 27449134
Shikazono, N. & Akamatsu, K. Strand with mutagenic lesion is preferentially used as a template in the region of a bi-stranded clustered DNA damage site in Escherichia coli. Sci. Rep. 10, 9737. https://doi.org/10.1038/s41598-020-66651-0 (2020).
doi: 10.1038/s41598-020-66651-0 pubmed: 32546758 pmcid: 7297740
Kuzminov, A. Single-strand interruptions in replicating chromosomes cause double-strand breaks. Proc. Natl. Acad. Sci. USA 98, 8241–8246. https://doi.org/10.1073/pnas.131009198 (2001).
doi: 10.1073/pnas.131009198 pubmed: 11459959 pmcid: 37427
Kouzminova, E. A. & Kuzminov, A. Fragmentation of replicating chromosomes triggered by uracil in DNA. J. Mol. Biol. 355, 20–33. https://doi.org/10.1016/j.jmb.2005.10.044 (2006).
doi: 10.1016/j.jmb.2005.10.044 pubmed: 16297932
Mahaseth, T. & Kuzminov, A. Prompt repair of hydrogen peroxide-induced DNA lesions prevents catastrophic chromosomal fragmentation. DNA Repair (Amst) 41, 42–53. https://doi.org/10.1016/j.dnarep.2016.03.012 (2016).
doi: 10.1016/j.dnarep.2016.03.012 pubmed: 27078578
Michel, B., Sinha, A. K. & Leach, D. R. F. Replication fork breakage and restart in Escherichia coli. Microbiol. Mol. Biol. Rev. https://doi.org/10.1128/MMBR.00013-18 (2018).
doi: 10.1128/MMBR.00013-18 pubmed: 29898897 pmcid: 6094043
Kuzminov, A. Collapse and repair of replication forks in Escherichia coli. Mol. Microbiol. 16, 373–384. https://doi.org/10.1111/j.1365-2958.1995.tb02403.x (1995).
doi: 10.1111/j.1365-2958.1995.tb02403.x pubmed: 7565099
Kornberg, A. & Baker, T. A. DNA Replication 113–159 (University Science Books, 1992).
Friedberg, E. C. et al. DNA Repair and Mutagenesis 2nd edn. (ASM Press, 2006).
Vaisman, A. et al. Investigating the mechanisms of ribonucleotide excision repair in Escherichia coli. Mutat. Res. 761, 21–33. https://doi.org/10.1016/j.mrfmmm.2014.01.005 (2014).
doi: 10.1016/j.mrfmmm.2014.01.005 pubmed: 24495324 pmcid: 4089967
Dianov, G. & Lindahl, T. Reconstitution of the DNA base excision-repair pathway. Curr. Biol. 4, 1069–1076. https://doi.org/10.1016/s0960-9822(00)00245-1 (1994).
doi: 10.1016/s0960-9822(00)00245-1 pubmed: 7535646
Sung, J. S. & Mosbaugh, D. W. Escherichia coli uracil- and ethenocytosine-initiated base excision DNA repair: Rate-limiting step and patch size distribution. Biochemistry 42, 4613–4625. https://doi.org/10.1021/bi027115v (2003).
doi: 10.1021/bi027115v pubmed: 12705824
Setlow, P., Brutlag, D. & Kornberg, A. Deoxyribonucleic acid polymerase: Two distinct enzymes in one polypeptide. I. A proteolytic fragment containing the polymerase and 3′ leads to 5′ exonuclease functions. J. Biol. Chem. 247, 224–231 (1972).
doi: 10.1016/S0021-9258(19)45779-7 pubmed: 4552924
Setlow, P. & Kornberg, A. Deoxyribonucleic acid polymerase: Two distinct enzymes in one polypeptide. II. A proteolytic fragment containing the 5′ leads to 3′ exonuclease function. Restoration of intact enzyme functions from the two proteolytic fragments. J. Biol. Chem. 247, 232–240 (1972).
doi: 10.1016/S0021-9258(19)45780-3 pubmed: 4552925
Patel, P. H., Suzuki, M., Adman, E., Shinkai, A. & Loeb, L. A. Prokaryotic DNA polymerase I: Evolution, structure, and “base flipping” mechanism for nucleotide selection. J. Mol. Biol. 308, 823–837. https://doi.org/10.1006/jmbi.2001.4619 (2001).
doi: 10.1006/jmbi.2001.4619 pubmed: 11352575
Polesky, A. H., Steitz, T. A., Grindley, N. D. & Joyce, C. M. Identification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli. J. Biol. Chem. 265, 14579–14591 (1990).
doi: 10.1016/S0021-9258(18)77342-0 pubmed: 2201688
Xu, Y. et al. Biochemical and mutational studies of the 5′–3′ exonuclease of DNA polymerase I of Escherichia coli. J. Mol. Biol. 268, 284–302. https://doi.org/10.1006/jmbi.1997.0967 (1997).
doi: 10.1006/jmbi.1997.0967 pubmed: 9159471
Xu, Y., Potapova, O., Leschziner, A. E., Grindley, N. D. & Joyce, C. M. Contacts between the 5′ nuclease of DNA polymerase I and its DNA substrate. J. Biol. Chem. 276, 30167–30177. https://doi.org/10.1074/jbc.M100985200 (2001).
doi: 10.1074/jbc.M100985200 pubmed: 11349126
Derbyshire, V. et al. Genetic and crystallographic studies of the 3′,5′-exonucleolytic site of DNA polymerase I. Science 240, 199–201. https://doi.org/10.1126/science.2832946 (1988).
doi: 10.1126/science.2832946 pubmed: 2832946
Singh, K., Srivastava, A., Patel, S. S. & Modak, M. J. Participation of the fingers subdomain of Escherichia coli DNA polymerase I in the strand displacement synthesis of DNA. J. Biol. Chem. 282, 10594–10604. https://doi.org/10.1074/jbc.M611242200 (2007).
doi: 10.1074/jbc.M611242200 pubmed: 17259182
Joyce, C. M., Fujii, D. M., Laks, H. S., Hughes, C. M. & Grindley, N. D. Genetic mapping and DNA sequence analysis of mutations in the polA gene of Escherichia coli. J. Mol. Biol. 186, 283–293. https://doi.org/10.1016/0022-2836(85)90105-6 (1985).
doi: 10.1016/0022-2836(85)90105-6 pubmed: 3910840
Heijneker, H. L. et al. A mutant of Escherichia coli K12 deficient in the 5′–3′ exonucleolytic activity of DNA polymerase I. II. Purification and properties of the mutant enzyme. Mol. Gen. Genet. 124, 83–96. https://doi.org/10.1007/BF00267167 (1973).
doi: 10.1007/BF00267167 pubmed: 4582300
Makiela-Dzbenska, K. et al. Role of Escherichia coli DNA polymerase I in chromosomal DNA replication fidelity. Mol. Microbiol. 74, 1114–1127. https://doi.org/10.1111/j.1365-2958.2009.06921.x (2009).
doi: 10.1111/j.1365-2958.2009.06921.x pubmed: 19843230 pmcid: 2818720
Parker, B. O. & Marinus, M. G. Repair of DNA heteroduplexes containing small heterologous sequences in Escherichia coli. Proc. Natl. Acad. Sci. USA 89, 1730–1734. https://doi.org/10.1073/pnas.89.5.1730 (1992).
doi: 10.1073/pnas.89.5.1730 pubmed: 1542666 pmcid: 48526
Shikazono, N. & O’Neill, P. Biological consequences of potential repair intermediates of clustered base damage site in Escherichia coli. Mutat. Res. 669, 162–168. https://doi.org/10.1016/j.mrfmmm.2009.06.004 (2009).
doi: 10.1016/j.mrfmmm.2009.06.004 pubmed: 19540248
Luisi-DeLuca, C. & Kolodner, R. Purification and characterization of the Escherichia coli RecO protein. Renaturation of complementary single-stranded DNA molecules catalyzed by the RecO protein. J. Mol. Biol. 236, 124–138. https://doi.org/10.1006/jmbi.1994.1123 (1994).
doi: 10.1006/jmbi.1994.1123 pubmed: 8107098
Hall, S. D. & Kolodner, R. D. Homologous pairing and strand exchange promoted by the Escherichia coli RecT protein. Proc. Natl. Acad. Sci. USA 91, 3205–3209. https://doi.org/10.1073/pnas.91.8.3205 (1994).
doi: 10.1073/pnas.91.8.3205 pubmed: 8159725 pmcid: 43544
Kuzminov, A. Recombinational repair of DNA damage in Escherichia coli and bacteriophage lambda. Microbiol. Mol. Biol. Rev. 63, 751–813. https://doi.org/10.1128/MMBR.63.4.751-813.1999 (1999) (table of contents).
doi: 10.1128/MMBR.63.4.751-813.1999 pubmed: 10585965 pmcid: 98976
Cupples, C. G. & Miller, J. H. A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc. Natl. Acad. Sci. USA 86, 5345–5349. https://doi.org/10.1073/pnas.86.14.5345 (1989).
doi: 10.1073/pnas.86.14.5345 pubmed: 2501784 pmcid: 297618
Kolodner, R., Hall, S. D. & Luisi-DeLuca, C. Homologous pairing proteins encoded by the Escherichia coli recE and recT genes. Mol. Microbiol. 11, 23–30. https://doi.org/10.1111/j.1365-2958.1994.tb00286.x (1994).
doi: 10.1111/j.1365-2958.1994.tb00286.x pubmed: 8145642
Shikazono, N. & Akamatsu, K. Mutagenic potential of 8-oxo-7,8-dihydroguanine (8-oxoG) is influenced by nearby clustered lesions. Mutat. Res. 810, 6–12. https://doi.org/10.1016/j.mrfmmm.2018.05.001 (2018).
doi: 10.1016/j.mrfmmm.2018.05.001 pubmed: 29870902
Lovett, S. T. Template-switching during replication fork repair in bacteria. DNA Repair (Amst) 56, 118–128. https://doi.org/10.1016/j.dnarep.2017.06.014 (2017).
doi: 10.1016/j.dnarep.2017.06.014 pubmed: 28641943
Maslowska, K. H., Makiela-Dzbenska, K., Mo, J. Y., Fijalkowska, I. J. & Schaaper, R. M. High-accuracy lagging-strand DNA replication mediated by DNA polymerase dissociation. Proc. Natl. Acad. Sci. USA 115, 4212–4217. https://doi.org/10.1073/pnas.1720353115 (2018).
doi: 10.1073/pnas.1720353115 pubmed: 29610333 pmcid: 5910852
Mourgues, S., Lomax, M. E. & O’Neill, P. Base excision repair processing of abasic site/single-strand break lesions within clustered damage sites associated with XRCC1 deficiency. Nucleic Acids Res. 35, 7676–7687 (2007).
doi: 10.1093/nar/gkm947 pubmed: 17982170 pmcid: 2190709
Radicella, J. P., Clark, E. A., Chen, S. & Fox, M. S. Patch length of localized repair events: Role of DNA polymerase I in mutY-dependent mismatch repair. J. Bacteriol. 175, 7732–7736. https://doi.org/10.1128/jb.175.23.7732-7736.1993 (1993).
doi: 10.1128/jb.175.23.7732-7736.1993 pubmed: 8244947 pmcid: 206937
Bhardwaj, A., Ghose, D., Thakur, K. G. & Dutta, D. Escherichia coli beta-clamp slows down DNA polymerase I dependent nick translation while accelerating ligation. PLoS One 13, e0199559. https://doi.org/10.1371/journal.pone.0199559 (2018).
doi: 10.1371/journal.pone.0199559 pubmed: 29924849 pmcid: 6010275
Taylor, A. F. & Weiss, B. Role of exonuclease III in the base excision repair of uracil-containing DNA. J. Bacteriol. 151, 351–357. https://doi.org/10.1128/jb.151.1.351-357.1982 (1982).
doi: 10.1128/jb.151.1.351-357.1982 pubmed: 6282808 pmcid: 220247
Demple, B. & Harrison, L. Repair of oxidative damage to DNA: Enzymology and biology. Annu. Rev. Biochem. 63, 915–948. https://doi.org/10.1146/annurev.bi.63.070194.004411 (1994).
doi: 10.1146/annurev.bi.63.070194.004411 pubmed: 7979257
Woodrick, J. et al. A new sub-pathway of long-patch base excision repair involving 5′ gap formation. EMBO J. 36, 1605–1622. https://doi.org/10.15252/embj.201694920 (2017).
doi: 10.15252/embj.201694920 pubmed: 28373211 pmcid: 5452013
Dianov, G. et al. Release of 5′-terminal deoxyribose-phosphate residues from incised abasic sites in DNA by the Escherichia coli RecJ protein. Nucleic Acids Res. 22, 993–998. https://doi.org/10.1093/nar/22.6.993 (1994).
doi: 10.1093/nar/22.6.993 pubmed: 7512263 pmcid: 307920
Datsenko, K. A. & Wanner, B. L. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc. Natl. Acad. Sci. USA 97, 6640–6645. https://doi.org/10.1073/pnas.120163297 (2000).
doi: 10.1073/pnas.120163297 pubmed: 10829079 pmcid: 18686

Auteurs

Naoya Shikazono (N)

Kansai Institute for Photon Science, National Institutes for Quantum Science and Technology (QST), 8-1-7 Umemidai, Kizugawa, Kyoto, 619-0215, Japan. shikazono.naoya@qst.go.jp.

Ken Akamatsu (K)

Kansai Institute for Photon Science, National Institutes for Quantum Science and Technology (QST), 8-1-7 Umemidai, Kizugawa, Kyoto, 619-0215, Japan.

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