Sequestration of mammalian Rad51-recombination protein into micronuclei

被引:110
作者
Haaf, T
Raderschall, E
Reddy, G
Ward, DC
Radding, CM
Golub, EI
机构
[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[2] Pangene Corp, Menlo Pk, CA 94025 USA
[3] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
关键词
DNA repair; immunofluorescence; micronuclei; Rad51; repairosome;
D O I
10.1083/jcb.144.1.11
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The mammalian Rad51 protein is involved in homologous recombination and in DNA damage repair. Its nuclear distribution after DNA damage is highly dynamic, and distinct foci of Rad51 protein, distributed throughout the nuclear volume, are induced within a few hours after gamma irradiation; these-foci then coalesce into larger clusters. Rad51-positive cells do not undergo DNA replication. Rad51 foci colocalize with both replication protein A and sites of unscheduled DNA repair synthesis and may represent a nuclear domain for recombinational DNA repair. By 24 h postirradiation, most foci are sequestered into micronuclei or assembled into Rad51-coated DNA fibers. These micronuclei and DNA fibers display genome fragmentation typical of apoptotic cell death. Other repair proteins, such as Rad52 and Gadd45, are not eliminated from the nucleus. DNA double strand breaks in repair-deficient cells or induced by the clastogen etoposide are also accompanied by the sequestering of Rad51 protein before cell death. The spindle poison colcemid causes cell cycle arrest and Rad51-foci formation without directly damaging DNA. Collectively, these observations suggest that mammalian Rad51 protein associates with damaged DNA and/or with DNA that is temporarily or irreversibly unable to replicate and these foci may subsequently be eliminated from the nucleus.
引用
收藏
页码:11 / 20
页数:10
相关论文
共 61 条
  • [51] MICRONUCLEI INDUCED BY MODULATORS OF METHYLATION - ANALOGS OF 5-AZACYTIDINE
    STOPPER, H
    KORBER, C
    GIBIS, P
    SPENCER, DL
    CASPARY, WJ
    [J]. CARCINOGENESIS, 1995, 16 (07) : 1647 - 1650
  • [52] p53 is linked directly to homologous recombination processes via RAD51/RecA protein interaction
    Sturzbecher, HW
    Donzelmann, B
    Henning, W
    Knippschild, U
    Buchhop, S
    [J]. EMBO JOURNAL, 1996, 15 (08) : 1992 - 2002
  • [53] A single-stranded DNA-binding protein is needed for efficient presynaptic complex formation by the Saccharomyces cerevisiae Rad51 protein
    Sugiyama, T
    Zaitseva, EM
    Kowalczykowski, SC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (12) : 7940 - 7945
  • [54] CATALYSIS OF ATP-DEPENDENT HOMOLOGOUS DNA PAIRING AND STRAND EXCHANGE BY YEAST RAD51 PROTEIN
    SUNG, P
    [J]. SCIENCE, 1994, 265 (5176) : 1241 - 1243
  • [55] Tashiro S, 1996, ONCOGENE, V12, P2165
  • [56] Targeted disruption of the Rad51 gene leads to lethality in embryonic mice
    Tsuzuki, T
    Fujii, Y
    Sakumi, K
    Tominaga, Y
    Nakao, K
    Sekiguchi, M
    Matsushiro, A
    Yoshimura, Y
    Morita, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (13) : 6236 - 6240
  • [57] UCKER DS, 1991, NEW BIOL, V3, P103
  • [58] SENSITIVITY OF MICRONUCLEUS INDUCTION IN HUMAN-LYMPHOCYTES TO LOW-LET RADIATION QUALITIES - RBE AND CORRELATION OF RBE AND LET
    VERHAEGEN, F
    VRAL, A
    [J]. RADIATION RESEARCH, 1994, 139 (02) : 208 - 213
  • [59] Overexpression of Rad51 protein stimulates homologous recombination and increases resistance of mammalian cells to ionizing radiation
    Vispé, S
    Cazaux, C
    Lesca, C
    Defais, M
    [J]. NUCLEIC ACIDS RESEARCH, 1998, 26 (12) : 2859 - 2864
  • [60] Yamamoto A, 1996, MOL GEN GENET, V251, P1