Home LiteratureArticle Details
PMID: 11486038 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis.

Molecular and cellular biology ·Vol. 21 ·No. 17 ·2001-09-00 ·Pages 6006-16

Maser RS, Mirzoeva OK, Wells J, Olivares H, Williams BR, Zinkel RA, Farnham PJ, Petrini JH

Abstract

We show that the Mre11 complex associates with E2F family members via the Nbs1 N terminus. This association and Nbs1 phosphorylation are correlated with S-phase checkpoint proficiency, whereas neither is sufficient individually for checkpoint activation. The Nbs1 E2F interaction occurred near the Epstein-Barr virus origin of replication as well as near a chromosomal replication origin in the c-myc promoter region and was restricted to S-phase cells. The Mre11 complex colocalized with PCNA at replication forks throughout S phase, both prior to and coincident with the appearance of nascent DNA. These data suggest that the Mre11 complex suppresses genomic instability through its influence on both the regulation and progression of DNA replication.

MeSH Terms
Animals Binding Sites Cell Cycle Proteins Cell Line DNA Repair Enzymes DNA Replication DNA-Binding Proteins/metabolism E2F Transcription Factors HeLa Cells Humans MRE11 Homologue Protein Mice Nuclear Proteins/metabolism Phosphorylation S Phase Signal Transduction Transcription Factors/metabolism Tumor Cells, Cultured
Chemicals
Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors MRE11 protein, human Mre11a protein, mouse Nuclear Proteins Transcription Factors MRE11 Homologue Protein DNA Repair Enzymes
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Maser R S
Laboratory of Genetics, University of Wisconsin Medical School, 445 Henry Mall, Madison, WI 53706, USA.
Mirzoeva O K
Wells J
Olivares H
Williams B R
Zinkel R A
Farnham P J
Petrini J H
References (74)
74 references, click to expand
  1. The effects of ionizing radiation on DNA synthesis in eukaryotic cells.
    Int J Radiat Biol. 1999 Mar;75(3):267-83 PMID: 10203178
  2. The mammalian Mre11-Rad50-nbs1 protein complex: integration of functions in the cellular DNA-damage response.
    Am J Hum Genet. 1999 May;64(5):1264-9 PMID: 10205255
  3. The BRCT domain of the S. cerevisiae checkpoint protein Rad9 mediates a Rad9-Rad9 interaction after DNA damage.
    Curr Biol. 1999 May 20;9(10):551-4 PMID: 10339432
  4. Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex.
    Genes Dev. 1999 May 15;13(10):1276-88 PMID: 10346816
  5. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81 PMID: 10377422
  6. The Mre11-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Nov;19(11):7681-7 PMID: 10523656
  7. Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2.
    Nature. 1997 Apr 24;386(6627):804-10 PMID: 9126738
  8. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells.
    Nucleic Acids Res. 1997 Aug 1;25(15):2985-91 PMID: 9224597
  9. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism.
    Cell. 1997 Jul 11;90(1):87-96 PMID: 9230305
  10. The timing of the formation and usage of replicase clusters in S-phase nuclei of human diploid fibroblasts.
    J Cell Sci. 1991 Dec;100 ( Pt 4):869-76 PMID: 1687687
  11. hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.
    Mol Cell Biol. 1997 Oct;17(10):6087-96 PMID: 9315668
  12. S phase damage sensing checkpoints in mammalian cells.
    Cancer Surv. 1997;29:25-45 PMID: 9338095
  13. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death.
    EMBO J. 1998 Jan 15;17(2):598-608 PMID: 9430650
  14. Initiation of DNA replication in eukaryotic cells.
    Annu Rev Cell Dev Biol. 1997;13:293-332 PMID: 9442876
  15. Mutations in the MRE11, RAD50, XRS2, and MRE2 genes alter chromatin configuration at meiotic DNA double-stranded break sites in premeiotic and meiotic cells.
    Proc Natl Acad Sci U S A. 1998 Jan 20;95(2):646-51 PMID: 9435246
  16. Cell cycle control of chorion gene amplification.
    Genes Dev. 1998 Mar 1;12(5):734-44 PMID: 9499407
  17. In situ visualization of DNA double-strand break repair in human fibroblasts.
    Science. 1998 Apr 24;280(5363):590-2 PMID: 9554850
  18. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.
    Cell. 1998 May 1;93(3):467-76 PMID: 9590180
  19. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.
    Cell. 1998 May 1;93(3):477-86 PMID: 9590181
  20. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks.
    Mol Cell. 1998 Jun;1(7):969-79 PMID: 9651580
  21. Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.
    EMBO J. 1999 Dec 1;18(23):6619-29 PMID: 10581236
  22. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.
    Cell. 1999 Dec 10;99(6):577-87 PMID: 10612394
  23. Replication fork pausing and recombination or "gimme a break".
    Genes Dev. 2000 Jan 1;14(1):1-10 PMID: 10640269
  24. The importance of repairing stalled replication forks.
    Nature. 2000 Mar 2;404(6773):37-41 PMID: 10716434
  25. PriA-directed replication fork restart in Escherichia coli.
    Trends Biochem Sci. 2000 Apr;25(4):185-9 PMID: 10754552
  26. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.
    Nature. 2000 Apr 6;404(6778):613-7 PMID: 10766245
  27. The Mre11 complex and ATM: collaborating to navigate S phase.
    Curr Opin Cell Biol. 2000 Jun;12(3):293-6 PMID: 10801460
  28. ATM-dependent phosphorylation of nibrin in response to radiation exposure.
    Nat Genet. 2000 May;25(1):115-9 PMID: 10802669
  29. Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products.
    Nature. 2000 May 25;405(6785):473-7 PMID: 10839544
  30. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response.
    Nature. 2000 May 25;405(6785):477-82 PMID: 10839545
  31. Major DNA replication initiation sites in the c-myc locus in human cells.
    J Cell Biochem. 2000 Jun 6;78(3):442-57 PMID: 10861842
  32. Initiation of eukaryotic DNA replication: conservative or liberal?
    J Cell Physiol. 2000 Aug;184(2):139-50 PMID: 10867638
  33. DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters.
    Nat Genet. 2000 Jul;25(3):338-42 PMID: 10888886
  34. Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human telomeres.
    Nat Genet. 2000 Jul;25(3):347-52 PMID: 10888888
  35. DNA damage-dependent nuclear dynamics of the Mre11 complex.
    Mol Cell Biol. 2001 Jan;21(1):281-8 PMID: 11113202
  36. Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice.
    Curr Biol. 2001 Jan 23;11(2):105-9 PMID: 11231126
  37. DNA replication control through interaction of E2F-RB and the origin recognition complex.
    Nat Cell Biol. 2001 Mar;3(3):289-95 PMID: 11231579
  38. An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele.
    Nat Genet. 2001 Apr;27(4):417-21 PMID: 11279524
  39. A DNA damage response pathway controlled by Tel1 and the Mre11 complex.
    Mol Cell. 2001 Jun;7(6):1255-66 PMID: 11430828
  40. Radioresistant DNA synthesis: an intrinsic feature of ataxia telangiectasia.
    Mutat Res. 1981 Nov;84(1):183-90 PMID: 7329432
  41. Hypersensitivity to ionizing radiation, in vitro, in a new chromosomal breakage disorder, the Nijmegen Breakage Syndrome.
    Mutat Res. 1983 Feb;112(1):23-32 PMID: 6828038
  42. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells.
    Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806-10 PMID: 6328526
  43. Further delineation of the Nijmegen breakage syndrome.
    Am J Med Genet. 1989 Mar;32(3):425-31 PMID: 2786340
  44. Inhibition of DNA replication by ionizing radiation is mediated by a trans-acting factor.
    Int J Radiat Biol. 1989 Aug;56(2):125-30 PMID: 2569014
  45. Immunolocalization in three dimensions: immunogold staining of cytoskeletal and nuclear matrix proteins in resinless electron microscopy sections.
    Proc Natl Acad Sci U S A. 1990 Mar;87(6):2259-63 PMID: 2315318
  46. Epstein-Barr virus-derived plasmids replicate only once per cell cycle and are not amplified after entry into cells.
    J Virol. 1991 Jan;65(1):483-8 PMID: 1845903
  47. Replication of chromosomal and episomal DNA in X-ray-damaged human cells: a cis- or trans-acting mechanism?
    Radiat Res. 1990 Dec;124(3):294-9 PMID: 2175922
  48. Drosophila chorion genes: cracking the eggshell's secrets.
    Bioessays. 1991 Mar;13(3):97-105 PMID: 1908228
  49. Ethidium bromide provides a simple tool for identifying genuine DNA-independent protein associations.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6958-62 PMID: 1495986
  50. The retinoblastoma protein binds to a family of E2F transcription factors.
    Mol Cell Biol. 1993 Dec;13(12):7813-25 PMID: 8246996
  51. Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair.
    Bioessays. 1994 Dec;16(12):893-900 PMID: 7840768
  52. A single ataxia telangiectasia gene with a product similar to PI-3 kinase.
    Science. 1995 Jun 23;268(5218):1749-53 PMID: 7792600
  53. Cellular targets for activation by the E2F1 transcription factor include DNA synthesis- and G1/S-regulatory genes.
    Mol Cell Biol. 1995 Aug;15(8):4215-24 PMID: 7623816
  54. DNA ligase I mediates essential functions in mammalian cells.
    Mol Cell Biol. 1995 Aug;15(8):4303-8 PMID: 7623824
  55. The FHA domain: a putative nuclear signalling domain found in protein kinases and transcription factors.
    Trends Biochem Sci. 1995 Sep;20(9):347-9 PMID: 7482699
  56. Introduction to the E2F family: protein structure and gene regulation.
    Curr Top Microbiol Immunol. 1996;208:1-30 PMID: 8575210
  57. Targeted disruption of the Rad51 gene leads to lethality in embryonic mice.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6236-40 PMID: 8692798
  58. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53.
    Mol Cell Biol. 1996 Dec;16(12):7133-43 PMID: 8943369
  59. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.
    FEBS Lett. 1997 Jan 2;400(1):25-30 PMID: 9000507
  60. Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites.
    J Cell Biol. 1987 Oct;105(4):1549-54 PMID: 2889739
  61. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
    FASEB J. 1997 Jan;11(1):68-76 PMID: 9034168
  62. Myc versus USF: discrimination at the cad gene is determined by core promoter elements.
    Mol Cell Biol. 1997 May;17(5):2529-37 PMID: 9111322
  63. The SbcCD nuclease of Escherichia coli is a structural maintenance of chromosomes (SMC) family protein that cleaves hairpin DNA.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):7969-74 PMID: 9653124
  64. Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint.
    Science. 1998 Jul 10;281(5374):272-4 PMID: 9657725
  65. The regulation of E2F by pRB-family proteins.
    Genes Dev. 1998 Aug 1;12(15):2245-62 PMID: 9694791
  66. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95.
    J Biol Chem. 1998 Aug 21;273(34):21447-50 PMID: 9705271
  67. The plasmid replicon of EBV consists of multiple cis-acting elements that facilitate DNA synthesis by the cell and a viral maintenance element.
    EMBO J. 1998 Nov 2;17(21):6394-403 PMID: 9799247
  68. Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination.
    EMBO J. 1998 Nov 2;17(21):6412-25 PMID: 9799249
  69. RuvAB acts at arrested replication forks.
    Cell. 1998 Oct 30;95(3):419-30 PMID: 9814711
  70. c-Myc target gene specificity is determined by a post-DNAbinding mechanism.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13887-92 PMID: 9811896
  71. The many interfaces of Mre11.
    Cell. 1998 Nov 25;95(5):583-6 PMID: 9845359
  72. Radiation down-regulates replication origin activity throughout the S phase in mammalian cells.
    Nucleic Acids Res. 1999 Feb 1;27(3):803-9 PMID: 9889276
  73. Double-strand break repair in yeast requires both leading and lagging strand DNA polymerases.
    Cell. 1999 Feb 5;96(3):415-24 PMID: 10025407
  74. ORC localization in Drosophila follicle cells and the effects of mutations in dE2F and dDP.
    Genes Dev. 1999 Apr 1;13(7):827-40 PMID: 10197983
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
2001-09-00
Pages
6006-16
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC87318
Subset
IM
Grants
NIGMS NIH HHS · R37 GM059413 · United States
NIGMS NIH HHS · GM59413 · United States
NCI NIH HHS · CA45240 · United States
NIGMS NIH HHS · R01 GM059413 · United States
NCI NIH HHS · CA09681 · United States
NCI NIH HHS · T32 CA009681 · United States
NCI NIH HHS · R01 CA045240 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com