Genetic analysis of BRCA1 function in a defined tumor cell line

Genetic analysis of BRCA1 function in a defined tumor cell line
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DOI:
10.1016/s1097-2765(00)80238-5
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发表时间:
1999-12-01
期刊:
影响因子:
16
通讯作者:
Livingston, DM
Livingston, DM
中科院分区:
生物学1区
文献类型:
--
作者:
Scully, R;Ganesan, S;Livingston, DM

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逆转录病毒表达的野生型 BRCA1 降低了 BRCA1(-/-) 人类乳腺癌系 HCC1937 的伽马辐射 (IR) 敏感性,并提高了双链 DNA 断裂修复 (DSBR) 的效率。它还降低了对 IR 产生 DSB 的敏感性。相比之下,多个经过临床验证的错义突变 BRCA1 产品在这些检测中没有功能。这些数据构成了 BRCA1 功能测定的基础,并表明双链 DNA 断裂的有效修复与 BRCA1 肿瘤抑制功能有关。
Retrovirally expressed, wild-type BRCA1 decreased the gamma radiation (IR) sensitivity and increased the efficiency of double-strand DNA break repair (DSBR) of the BRCA1(-/-) human breast cancer line, HCC1937. It also reduced its susceptibility to DSB generation by IR. By contrast, multiple, clinically validated, missense mutant BRCA1 products were nonfunctional in these assays. These data constitute the basis for a BRCA1 functional assay and suggest that efficient repair of double-strand DNA breaks is linked to BRCA1 tumor suppression function.