Essential Role of BRCA2 in Ovarian Development and Function.
Essential Role of BRCA2 in Ovarian Development and Function.
复制标题
DOI：
10.1056/nejmoa1800024
复制
发表时间：
2018-09-13
期刊：
影响因子：
--
通讯作者：
Zangen D
中科院分区：
文献类型：
--
作者：
Weinberg-Shukron A;Rachmiel M;Renbaum P;Gulsuner S;Walsh T;Lobel O;Dreifuss A;Ben-Moshe A;Zeligson S;Segel R;Shore T;Kalifa R;Goldberg M;King MC;Gerlitz O;Levy-Lahad E;Zangen D
卵巢发育不全的原因仍不完全清楚。两个XX卵巢发育不全的姐妹携带BRCA2基因的复合杂合截断突变，导致BRCA2蛋白水平降低，对DNA损伤的反应减弱，导致染色体断裂和RAD51无法被招募到双链DNA断裂。这对姐妹还患有小头畸形症，其中一个姐妹的白血病长期缓解，她在5岁时就被诊断出患有白血病。BRCA2同源基因缺失的果蝇突变体是不育的，性腺发育不全在两性中都存在。这些结果揭示了BRCA2的新作用，并强调了在减数分裂过程中对重组至关重要的基因对卵巢发育的重要性。(由以色列科学基金会和其他机构资助。)
The causes of ovarian dysgenesis remain incompletely understood. Two sisters with XX ovarian dysgenesis carried compound heterozygous truncating mutations in the BRCA2 gene that led to reduced BRCA2 protein levels and an impaired response to DNA damage, which resulted in chromosomal breakage and the failure of RAD51 to be recruited to double-stranded DNA breaks. The sisters also had microcephaly, and one sister was in long-term remission from leukemia, which had been diagnosed when she was 5 years old. Drosophila mutants that were null for an orthologue of BRCA2 were sterile, and gonadal dysgenesis was present in both sexes. These results revealed a new role for BRCA2 and highlight the importance to ovarian development of genes that are critical for recombination during meiosis. (Funded by the Israel Science Foundation and others.)