Dual roles of yeast Rad51 N-terminal domain in repairing DNA double-strand breaks.
DNA Breaks, Double-Stranded
DNA Damage
/ genetics
DNA Repair
/ genetics
DNA-Binding Proteins
/ genetics
Endodeoxyribonucleases
/ genetics
Gene Expression Regulation, Fungal
/ genetics
Intracellular Signaling Peptides and Proteins
/ genetics
Meiosis
/ genetics
Phosphorylation
/ genetics
Proteasome Endopeptidase Complex
/ genetics
Protein Domains
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Proteolysis
Rad51 Recombinase
/ genetics
Saccharomyces cerevisiae
/ genetics
Saccharomyces cerevisiae Proteins
/ genetics
beta-Galactosidase
/ genetics
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
accepted:
03
07
2020
revised:
24
06
2020
received:
22
10
2019
pubmed:
12
7
2020
medline:
21
10
2020
entrez:
12
7
2020
Statut:
ppublish
Résumé
Highly toxic DNA double-strand breaks (DSBs) readily trigger the DNA damage response (DDR) in cells, which delays cell cycle progression to ensure proper DSB repair. In Saccharomyces cerevisiae, mitotic S phase (20-30 min) is lengthened upon DNA damage. During meiosis, Spo11-induced DSB onset and repair lasts up to 5 h. We report that the NH2-terminal domain (NTD; residues 1-66) of Rad51 has dual functions for repairing DSBs during vegetative growth and meiosis. Firstly, Rad51-NTD exhibits autonomous expression-enhancing activity for high-level production of native Rad51 and when fused to exogenous β-galactosidase in vivo. Secondly, Rad51-NTD is an S/T-Q cluster domain (SCD) harboring three putative Mec1/Tel1 target sites. Mec1/Tel1-dependent phosphorylation antagonizes the proteasomal degradation pathway, increasing the half-life of Rad51 from ∼30 min to ≥180 min. Our results evidence a direct link between homologous recombination and DDR modulated by Rad51 homeostasis.
Identifiants
pubmed: 32652040
pii: 5870334
doi: 10.1093/nar/gkaa587
pmc: PMC7470947
doi:
Substances chimiques
DNA-Binding Proteins
0
Intracellular Signaling Peptides and Proteins
0
Saccharomyces cerevisiae Proteins
0
MEC1 protein, S cerevisiae
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
TEL1 protein, S cerevisiae
EC 2.7.11.1
RAD51 protein, S cerevisiae
EC 2.7.7.-
Rad51 Recombinase
EC 2.7.7.-
Endodeoxyribonucleases
EC 3.1.-
Spo11 protein, S cerevisiae
EC 3.1.-
beta-Galactosidase
EC 3.2.1.23
Proteasome Endopeptidase Complex
EC 3.4.25.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8474-8489Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
Références
J Biol Chem. 2007 Jan 12;282(2):986-95
pubmed: 17114794
Cold Spring Harb Symp Quant Biol. 1974;38:195-203
pubmed: 4598637
J Biol Chem. 1999 Dec 31;274(53):37538-43
pubmed: 10608806
J Mol Biol. 2019 Apr 5;431(8):1650-1670
pubmed: 30878482
Cold Spring Harb Perspect Biol. 2014 Dec 04;7(1):a016659
pubmed: 25475089
Cell. 1991 Sep 20;66(6):1239-56
pubmed: 1913808
Cell. 2008 Mar 7;132(5):758-70
pubmed: 18329363
Cell. 2001 Jul 13;106(1):59-70
pubmed: 11461702
Cold Spring Harb Perspect Biol. 2015 Nov 02;7(11):
pubmed: 26525148
Mol Cell Biol. 2013 Aug;33(16):3365-76
pubmed: 23775120
Genes Dev. 1999 Apr 15;13(8):916-34
pubmed: 10215620
Methods Mol Biol. 2011;745:99-116
pubmed: 21660691
PLoS Genet. 2013 Jun;9(6):e1003545
pubmed: 23825959
Nat Rev Mol Cell Biol. 2008 Aug;9(8):616-27
pubmed: 18594563
Annu Rev Genet. 1999;33:603-754
pubmed: 10690419
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13749-54
pubmed: 11095737
Genes Dev. 2006 Aug 1;20(15):2067-81
pubmed: 16847351
Mol Biol Evol. 2013 Apr;30(4):772-80
pubmed: 23329690
Methods Mol Biol. 2009;557:209-34
pubmed: 19799185
Cell Cycle. 2006 Jul;5(14):1549-59
pubmed: 16861895
Nucleic Acids Res. 2016 Sep 19;44(16):7722-41
pubmed: 27257060
Genes Dev. 2006 Jul 1;20(13):1766-75
pubmed: 16818607
Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10814-9
pubmed: 11005857
Genes Dev. 2000 Feb 15;14(4):493-503
pubmed: 10691741
Bioessays. 2005 Apr;27(4):397-407
pubmed: 15770685
Mol Cell Biol. 2003 Sep;23(17):6300-14
pubmed: 12917350
EMBO Rep. 2011 Jul 08;12(8):833-9
pubmed: 21738226
Chromosome Res. 2007;15(5):539-50
pubmed: 17674144
Genes Dev. 2008 Mar 15;22(6):786-95
pubmed: 18347097
Cold Spring Harb Perspect Biol. 2015 Oct 28;7(12):
pubmed: 26511629
Cell Syst. 2018 Feb 28;6(2):192-205.e3
pubmed: 29361465
Trends Biochem Sci. 2006 Jul;31(7):402-10
pubmed: 16774833
Genes Dev. 1994 Mar 15;8(6):652-65
pubmed: 7926756
Mol Cell. 2015 Mar 5;57(5):797-811
pubmed: 25661491
Science. 2015 Aug 28;349(6251):977-81
pubmed: 26315438
Cell. 2015 Feb 26;160(5):856-869
pubmed: 25684365
Genetics. 2002 Jun;161(2):493-507
pubmed: 12072449
Science. 2012 Sep 7;337(6099):1222-5
pubmed: 22955832
Mol Cell. 1998 Sep;2(3):329-40
pubmed: 9774971
J Biol Chem. 1999 Dec 17;274(51):36679-83
pubmed: 10593972
Nucleic Acids Res. 2012 Dec;40(22):11416-27
pubmed: 23047948
Curr Genet. 2019 Jun;65(3):657-661
pubmed: 30610294
Mol Cell. 2009 Nov 13;36(3):393-404
pubmed: 19917248
Dev Cell. 2010 Oct 19;19(4):599-611
pubmed: 20951350
Mol Cell. 2007 Aug 17;27(4):660-74
pubmed: 17707236
Nucleic Acids Res. 1997 May 15;25(10):2035-6
pubmed: 9115375
Mol Cell. 2007 Dec 14;28(5):739-45
pubmed: 18082599
Nucleic Acids Res. 2001 Dec 1;29(23):4808-17
pubmed: 11726690
Cold Spring Harb Protoc. 2015 Nov 02;2015(11):1003-8
pubmed: 26527763
PLoS Genet. 2013;9(12):e1003978
pubmed: 24367271
Proc Natl Acad Sci U S A. 1977 Sep;74(9):3850-4
pubmed: 333447
Cold Spring Harb Perspect Biol. 2014 Sep 04;6(11):a017954
pubmed: 25190078
EMBO J. 2010 Feb 3;29(3):586-96
pubmed: 19959993
Cell. 1992 May 1;69(3):457-70
pubmed: 1581961
Dev Cell. 2018 Aug 20;46(4):495-503.e2
pubmed: 30130531
PLoS Genet. 2016 Aug 02;12(8):e1006226
pubmed: 27483004
Cell. 2006 Jul 28;126(2):285-95
pubmed: 16873061
Mol Cell. 2002 May;9(5):1055-65
pubmed: 12049741
Cold Spring Harb Perspect Biol. 2011 Jan 01;3(1):a000745
pubmed: 20980439
Cell. 1992 May 1;69(3):439-56
pubmed: 1581960
Mol Cell Biol. 1984 Nov;4(11):2529-31
pubmed: 6392855
PLoS One. 2014 Jan 21;9(1):e85687
pubmed: 24465650
BMC Genomics. 2012 Nov 23;13:664
pubmed: 23176708
PLoS One. 2012;7(6):e39724
pubmed: 22745819