Cutting edge:: DNA polymerases μ and λ are dispensable for Ig gene hypermutation

被引:113
作者
Bertocci, B
De Smet, A
Flatter, E
Dahan, A
Bories, JC
Landreau, C
Weill, JC
Reynaud, CA
机构
[1] CHU Necker Enfants Malad, Fac Med, Unite 373, Inst Natl St & Rech Med, F-75730 Paris 15, France
[2] Hop St Louis, Unite 462, Inst Natl St & Rech Med, Paris, France
[3] Ctr Natl Rech Sci, Serv Expt Anim & Transgenese, Villejuif, France
关键词
D O I
10.4049/jimmunol.168.8.3702
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mutations arising in Ig V genes during an immune response are most likely introduced by one or several error-prone DNA polymerases. Many of the recently described nonreplicative DNA polymerases have an intrinsic fidelity compatible with such an activity, the strongest candidates being polymerase (pol) eta, pol iota, pol zeta, and pol mu. We report in this work that mice inactivated for either of the two polymerases related to pol beta (i.e., pol mu and pol lambda) are viable and fertile and display a normal hypermutation pattern.
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页码:3702 / 3706
页数:5
相关论文
共 24 条
  • [1] Two novel human and mouse DNA polymerases of the polX family
    Aoufouchi, S
    Flatter, E
    Dahan, A
    Faili, A
    Bertocci, B
    Storck, S
    Delbos, F
    Cocea, L
    Gupta, N
    Weill, JC
    Reynaud, CA
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (18) : 3684 - 3693
  • [2] Probing immunoglobulin gene hypermutation with microsatellites suggests a nonreplicative short patch DNA synthesis process
    Bertocci, B
    Quint, L
    Delbos, F
    Garcia, C
    Reynaud, CA
    Weill, JC
    [J]. IMMUNITY, 1998, 9 (02) : 257 - 265
  • [3] A superfamily of conserved domains in DNA damage responsive cell cycle checkpoint proteins
    Bork, P
    Hofmann, K
    Bucher, P
    Neuwald, AF
    Altschul, SF
    Koonin, EV
    [J]. FASEB JOURNAL, 1997, 11 (01) : 68 - 76
  • [4] ORIGIN OF ANTIBODY VARIATION
    BRENNER, S
    MILSTEIN, C
    [J]. NATURE, 1966, 211 (5046) : 242 - &
  • [5] Decreased frequency of somatic hypermutation and impaired affinity maturation but intact germinal center formation in mice expressing antisense RNA to DNA polymerase ζ
    Diaz, M
    Verkoczy, LK
    Flajnik, MF
    Klinman, NR
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 167 (01) : 327 - 335
  • [6] DNA polymerase mu (Pol μ), homologous to TdT, could act as a DNA mutator in eukaryotic cells
    Domínguez, O
    Ruiz, JF
    de Lera, TL
    García-Díaz, M
    González, MA
    Kirchhoff, T
    Martínez-A, C
    Bernad, A
    Blanco, L
    [J]. EMBO JOURNAL, 2000, 19 (07) : 1731 - 1742
  • [7] Mice reconstituted with DNA polymerase β-deficient fetal liver cells are able to mount a T cell-dependent immune response and mutate their Ig genes normally
    Esposito, G
    Texido, G
    Betz, UAK
    Gu, H
    Müller, W
    Klein, U
    Rajewsky, K
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (03) : 1166 - 1171
  • [8] Mismatch repair deficiency interferes with the accumulation of mutations in chronically stimulated B cells and not with the hypermutation process
    Frey, S
    Bertocci, B
    Delbos, F
    Quint, L
    Weill, JC
    Reynaud, CA
    [J]. IMMUNITY, 1998, 9 (01) : 127 - 134
  • [9] Identification of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in human DNA polymerase λ -: A possible role in base excision repair
    García-Díaz, M
    Bebenek, K
    Kunkel, TA
    Blanco, L
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (37) : 34659 - 34663
  • [10] DNA polymerase lambda (Pol λ), a novel eukaryotic DNA polymerase with a potential role in meiosis
    García-Díaz, M
    Domínguez, O
    López-Fernández, LA
    de Lera, LT
    Saníger, ML
    Ruiz, JF
    Párraga, M
    García-Ortiz, MJ
    Kirchhoff, T
    del Mazo, J
    Bernad, A
    Blanco, L
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2000, 301 (04) : 851 - 867