Mutations in the TP53 gene affected recruitment of 53BP1 protein to DNA lesions, but level of 53BP1 was stable after γ-irradiation that depleted MDC1 protein in specific TP53 mutants
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28397142
DOI
10.1007/s00418-017-1567-3
PII: 10.1007/s00418-017-1567-3
Knihovny.cz E-zdroje
- Klíčová slova
- 53BP1 protein, DNA repair, Histone γH2AX, MDC1 protein, TP53 gene,
- MeSH
- 53BP1 metabolismus MeSH
- adaptorové proteiny signální transdukční MeSH
- down regulace MeSH
- jaderné proteiny nedostatek metabolismus MeSH
- lidé MeSH
- mutace * MeSH
- nádorové buňky kultivované MeSH
- nádorový supresorový protein p53 nedostatek genetika metabolismus MeSH
- poškození DNA * MeSH
- proteiny buněčného cyklu MeSH
- trans-aktivátory nedostatek metabolismus MeSH
- ultrafialové záření * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 53BP1 MeSH
- adaptorové proteiny signální transdukční MeSH
- jaderné proteiny MeSH
- MDC1 protein, human MeSH Prohlížeč
- nádorový supresorový protein p53 MeSH
- proteiny buněčného cyklu MeSH
- TP53 protein, human MeSH Prohlížeč
- TP53BP1 protein, human MeSH Prohlížeč
- trans-aktivátory MeSH
53BP1 is a very well-known protein that is recruited to DNA lesions. The focal accumulation of p53 binding protein, 53BP1, is a main feature indicating the repair of spontaneous or irradiation-induced foci (IRIF). Thus, here, we addressed the question of whether mutations in the TP53 gene, which often affect the level of p53 protein, can change the recruitment of 53BP1 to γ- or UVA-irradiated chromatin. In various TP53 mutants, we observed a distinct accumulation of 53BP1 protein to UV-induced DNA lesions: in R273C mutants, 53BP1 appeared transiently at DNA lesions, during 10-30 min after irradiation; the mutation R282W was responsible for accumulation of 53BP1 immediately after UVA-damage; and in L194F mutants, the first appearance of 53BP1 protein at the lesions occurred during 60-70 min. These results showed that specific mutations in the TP53 gene stand behind not only different levels of p53 protein, but also affect the localized kinetics of 53BP1 protein in UVA-damaged chromatin. However, after γ-irradiation, only G245S mutation in TP53 gene was associated with surprisingly decreased level of 53BP1 protein. In other mutant cell lines, levels of 53BP1 were not affected by γ-rays. To these effects, we conversely found a distinct number of 53BP1-positive irradiation-induced foci in various TP53 mutants. The R280K, G245S, L194F mutations, or TP53 deletion were also characterized by radiation-induced depletion in MDC1 protein. Moreover, in mutant cells, an interaction between MDC1 and 53BP1 proteins was abrogated when compared with wild-type counterpart. Together, the kinetics of 53BP1 accumulation at UV-induced DNA lesions is different in various TP53 mutant cells. After γ-irradiation, despite changes in a number and a volume of 53BP1-positive foci, levels of 53BP1 protein were relatively stable. Here, we showed a link between the status of MDC1 protein and TP53 gene, which specific mutations caused radiation-induced MDC1 down-regulation. This observation is significant, especially with regard to radiotherapy of tumors with abrogated function of TP53 gene.
Zobrazit více v PubMed
Gene. 2000 Feb 22;244(1-2):1-11 PubMed
Proc Natl Acad Sci U S A. 1985 Feb;82(3):790-4 PubMed
DNA Cell Biol. 2000 Aug;19(8):475-85 PubMed
Science. 1994 Jul 15;265(5170):346-55 PubMed
Cancer Res. 2003 Dec 15;63(24):8586-91 PubMed
Leuk Res. 2008 Dec;32(12):1866-77 PubMed
DNA Repair (Amst). 2004 Aug-Sep;3(8-9):953-7 PubMed
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6098-102 PubMed
Mol Cell. 2016 Oct 6;64(1):51-64 PubMed
Nat Rev Mol Cell Biol. 2009 Apr;10(4):243-54 PubMed
J Cell Biol. 2005 Jul 18;170(2):201-11 PubMed
J Biol Chem. 2005 Apr 22;280(16):16030-7 PubMed
Nat Rev Mol Cell Biol. 2014 Jan;15(1):7-18 PubMed
Cell. 2003 Aug 8;114(3):359-70 PubMed
Int J Biochem Cell Biol. 2012 Sep;44(9):1398-409 PubMed
Nature. 2003 Feb 27;421(6926):952-6 PubMed
J Cell Physiol. 2012 May;227(5):1838-50 PubMed
Leuk Res. 2005 Aug;29(8):901-13 PubMed
Nucleic Acids Res. 1994 Sep;22(17):3551-5 PubMed
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4035-9 PubMed
Cell Res. 2013 May;23(5):597-8 PubMed
Oncogene. 2007 Apr 2;26(15):2226-42 PubMed
PLoS One. 2013 Nov 29;8(11):e79541 PubMed
Structure. 2006 Dec;14 (12 ):1811-21 PubMed
Mol Cell Biol. 1984 Jul;4(7):1402-10 PubMed
Blood. 1992 May 1;79(9):2378-83 PubMed
Microsc Microanal. 2013 Apr;19(2):360-9 PubMed
J Biol Chem. 2008 Dec 12;283(50):34660-6 PubMed
Leukemia. 2002 Oct;16(10):2165-7 PubMed
Tumour Biol. 2013 Aug;34(4):2063-74 PubMed
Epigenetics Chromatin. 2014 Dec 30;7(1):39 PubMed
DNA Repair (Amst). 2004 Aug-Sep;3(8-9):945-52 PubMed
J Biol Chem. 2003 May 30;278(22):19579-82 PubMed
EMBO J. 2002 Jul 15;21(14 ):3863-72 PubMed
Mol Cell. 2006 Jun 23;22(6):741-53 PubMed
J Cell Biol. 2000 Dec 25;151(7):1381-90 PubMed
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3310-5 PubMed
Curr Biol. 2000 Apr 20;10 (8):R315-7 PubMed
Biochimie. 2013 Feb;95(2):167-79 PubMed
Nat Genet. 2001 Mar;27(3):247-54 PubMed
Cell. 2003 Aug 8;114(3):371-383 PubMed
Nature. 2003 Feb 27;421(6926):961-6 PubMed
Oncogene. 1990 Jul;5(7):945-52 PubMed
Nat Cell Biol. 2002 Dec;4(12 ):993-7 PubMed
J Cell Biol. 2009 May 18;185(4):577-86 PubMed
Biol Cell. 2015 Dec;107(12 ):440-54 PubMed
Genes Dev. 2002 Mar 1;16(5):583-93 PubMed
