The multiple roles of the Mre11 complex for meiotic recombination

被引:98
作者
Borde, Valerie [1 ]
机构
[1] Univ Paris 06, Inst Curie, CNRS, Inst Curie Recombinas & Instabilite Genet,Ctr Rec, F-75248 Paris 05, France
关键词
DNA damage checkpoint; double-strand breaks; meiosis; Mre; 11; Saccharomyces cerevisiae; yeast;
D O I
10.1007/s10577-007-1147-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
During the first meiotic prophase, numerous DNA double-strand breaks (DSB) are fon-ned in the genome in order to initiate recombination between homologous chromosomes. The conserved Mre11 complex, formed of Mre 11, Rad50 and Nbs1 (Xrs2 in Saccharonzyces cerevisiae) proteins, plays a crucial role in mitotic cells for sensing and repairing DSB. In meiosis the Mre11 complex is also required for meiotic recombination. Depending on the organisms, the Mre11complex is required for the formation of the DSB catalysed by the transesterase Spo11 protein. It then plays a unique function in removing covalently attached Spo11 from the 5' extremity of the breaks through its nuclease activity, to allow further break resection. Finally, the Mre11 complex also plays a role during meiosis in bridging DNA molecules together and in sensing Spo11 DSB and activating the DNA damage checkpoint. In this article the different biochemical functions of the Mre11complex required during meiosis are reviewed, as well as the consequences of Mre11complex inactivation for meiosis in several oroanisms. Finally, I describe the meiotic phenotypes of several animal models that have been developed to model hypornorphic mutations of the Mre11 complex, involved in humans in some genetic instability disorders.
引用
收藏
页码:551 / 563
页数:13
相关论文
共 82 条
  • [1] AJIMURA M, 1993, GENETICS, V133, P51
  • [2] ANALYSIS OF WILD-TYPE AND RAD50 MUTANTS OF YEAST SUGGESTS AN INTIMATE-RELATIONSHIP BETWEEN MEIOTIC CHROMOSOME SYNAPSIS AND RECOMBINATION
    ALANI, E
    PADMORE, R
    KLECKNER, N
    [J]. CELL, 1990, 61 (03) : 419 - 436
  • [4] Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism
    Arora, C
    Kee, K
    Maleki, S
    Keeney, S
    [J]. MOLECULAR CELL, 2004, 13 (04) : 549 - 559
  • [5] Cancer predisposition and hematopoietic failure in Rad50S/S mice
    Bender, CF
    Sikes, ML
    Sullivan, R
    Huye, LE
    Le Beau, MM
    Roth, DB
    Mirzoeva, OK
    Oltz, EM
    Petrini, JHJ
    [J]. GENES & DEVELOPMENT, 2002, 16 (17) : 2237 - 2251
  • [6] Rad50 adenylate kinase activity regulates DNA tethering by Mre11/Rad50 complexes
    Bhaskara, Venugopal
    Dupre, Aude
    Lengsfeld, Bettina
    Hopkins, Ben B.
    Chan, Angela
    Lee, Ji-Hoon
    Zhang, Xiaoming
    Gautier, Jean
    Zakian, Virginia
    Paull, Tanya T.
    [J]. MOLECULAR CELL, 2007, 25 (05) : 647 - 661
  • [7] Physical and functional interactions among basic chromosome organizational features govern early steps of meiotic chiasma formation
    Blat, Y
    Protacio, RU
    Hunter, N
    Kleckner, N
    [J]. CELL, 2002, 111 (06) : 791 - 802
  • [8] Meiotic defects in the Arabidopsis rad50 mutant point to conservation of the MRX complex function in early stages of meiotic recombination
    Bleuyard, JY
    Gallego, ME
    White, CI
    [J]. CHROMOSOMA, 2004, 113 (04) : 197 - 203
  • [9] Association of Mre11p with double-strand break sites during yeast meiosis
    Borde, V
    Lin, W
    Novikov, E
    Petrini, JH
    Lichten, M
    Nicolas, A
    [J]. MOLECULAR CELL, 2004, 13 (03) : 389 - 401
  • [10] Bressan DA, 1999, MOL CELL BIOL, V19, P7681