Positive role of the mammalian TBPIP/HOP2 protein in DMC1-mediated homologous pairing.
In meiosis, homologous recombination preferentially occurs between homologous chromosomes rather than between sister chromatids, which is opposite to the bias of mitotic recombinational repair. The TBPIP/HOP2 protein is a factor that ensures the proper pairing of homologous chromosomes during meiosis. In the present study, we found that the purified mouse TBPIP/HOP2 protein stimulated homologous pairing catalyzed by the meiotic DMC1 recombinase in vitro. In contrast, TBPIP/HOP2 did not stimulate homologous pairing by RAD51, which is another homologous pairing protein acting in both meiotic and mitotic recombination. The positive effect of TBPIP/HOP2 in the DMC1-mediated homologous pairing was only observed when TBPIP/HOP2 first binds to double-stranded DNA, not to single-stranded DNA, before the initiation of the homologous pairing reaction. Deletion analyses revealed that the C-terminal basic region of TBPIP/HOP2 is required for efficient DNA binding and is also essential for its homologous pairing stimulation activity. Therefore, these results suggest that TBPIP/HOP2 directly binds to DNA and functions as an activator for DMC1 during the homologous pairing step in meiosis.
Enomoto
Rima
R
RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
Kinebuchi
Takashi
T
Sato
Makoto
M
Yagi
Hideshi
H
Shibata
Takehiko
T
Kurumizaka
Hitoshi
H
Yokoyama
Shigeyuki
S
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D028044:Phosphate-Binding Proteins; D011485:Protein Binding; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C513032:Dmc1 protein, mouse; D009687:Nuclear Proteins; C443678:PSMC3IP protein, human; D028044:Phosphate-Binding Proteins; D015534:Trans-Activators; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D000251:Adenosine Triphosphatases; C074556:DMC1 protein, human