TY - JOUR
T1 - Conserved domains in the chicken homologue of BRCA2
AU - Takata, Minoru
AU - Tachiiri, Seiji
AU - Fujimori, Akira
AU - Thompson, Larry H.
AU - Miki, Yoshio
AU - Hiraoka, Masahiro
AU - Takeda, Shunichi
AU - Yamazoe, Mitsuyoshi
PY - 2002/2/7
Y1 - 2002/2/7
N2 - Germline mutation of the BRCA2 gene causes a high risk of developing breast and ovarian cancer. Although the BRCA2 protein has been implicated in homologous recombination (HR) of DNA and in transcription, it is still unclear how mutation leads to tumorigenesis. We have identified a nonmammalian homologue of BRCA2 from chicken, which encodes a protein with 3397 amino acids (aa) and shows only 40% identity to human BRCA2. However, comparison of the mammalian and chicken sequences revealed remarkably high homology in several segments. These include a N-terminal region (∼ 100 aa), which was previously shown to possess intrinsic transcriptional activity, and a C-terminal region (aa residue ∼ 2480- ∼ 3180 in human BRCA2), which has not been clearly assigned any function. In contrast, although the eight BRC repeats of mammalian BRCA2 are believed to play an important role in HR by interacting with Rad51, the BRC3, BRC5, and BRC6 repeats exhibit virtually no similarity to their mammalian counterparts. Among 311 missense mutations listed as unclassified variants in the NIH Breast Cancer Information Core database, only 83 of these sites are identical in chicken BRCA2. Thus, chicken BRCA2 may provide a means to identify domains and residues associated with cancer predisposition.
AB - Germline mutation of the BRCA2 gene causes a high risk of developing breast and ovarian cancer. Although the BRCA2 protein has been implicated in homologous recombination (HR) of DNA and in transcription, it is still unclear how mutation leads to tumorigenesis. We have identified a nonmammalian homologue of BRCA2 from chicken, which encodes a protein with 3397 amino acids (aa) and shows only 40% identity to human BRCA2. However, comparison of the mammalian and chicken sequences revealed remarkably high homology in several segments. These include a N-terminal region (∼ 100 aa), which was previously shown to possess intrinsic transcriptional activity, and a C-terminal region (aa residue ∼ 2480- ∼ 3180 in human BRCA2), which has not been clearly assigned any function. In contrast, although the eight BRC repeats of mammalian BRCA2 are believed to play an important role in HR by interacting with Rad51, the BRC3, BRC5, and BRC6 repeats exhibit virtually no similarity to their mammalian counterparts. Among 311 missense mutations listed as unclassified variants in the NIH Breast Cancer Information Core database, only 83 of these sites are identical in chicken BRCA2. Thus, chicken BRCA2 may provide a means to identify domains and residues associated with cancer predisposition.
KW - BRC repeat
KW - BRCA2
KW - Homologous recombination
KW - Rad51
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U2 - 10.1038/sj/onc/1205168
DO - 10.1038/sj/onc/1205168
M3 - Article
C2 - 11850831
VL - 21
SP - 1130
EP - 1134
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 7
ER -