Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.
Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.
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DOI：
10.1002/humu.22251
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发表时间：
2013-03
期刊：
影响因子：
3.9
通讯作者：
Parvin, Jeffrey D.
中科院分区：
文献类型：
--
作者：
Towler, William I.;Zhang, Jie;Ransburgh, Derek J. R.;Toland, Amanda E.;Ishioka, Chikashi;Chiba, Natsuko;Parvin, Jeffrey D.
对于有乳腺癌家族史的女性来说，BRCA1基因中临床意义不确定的错义替换是遗传咨询中的一个令人烦恼的问题。在本研究中，我们评估了BRCA1的29个错义替换在两条DNA修复途径中的作用。先前已经分析了16个BRCA1变异体通过同源定向重组(HDR)修复双链断裂，本研究还分析了另外13个变异体。通过单链退火(SSA)途径分析了所有29个突变体在双链断裂修复中的功能。我们发现，在BRCA1的致病突变中，无论通过哪一种途径，都存在DNA修复缺陷。HDR检测是准确的，因为所有致病突变体对HDR都是缺陷的，而所有非致病突变对HDR都是完全功能的。SSA修复准确鉴定了致病突变体，但几个非致病突变体被评为有缺陷或部分有缺陷。这些结果表明，BRCA1蛋白的特定氨基酸残基在两个相关的DNA修复途径中具有不同的作用，这些结果验证了HDR法与BRCA1相关乳腺癌的高度相关性。
Missense substitutions of uncertain clinical significance in the BRCA1 gene are a vexing problem in genetic counseling for women who have a family history of breast cancer. In this study, we evaluated the functions of 29 missense substitutions of BRCA1 in two DNA repair pathways. Repair of double-strand breaks by homology-directed recombination (HDR) had been previously analyzed for 16 of these BRCA1 variants, and 13 more variants were analyzed in this study. All 29 variants were also analyzed for function in double-strand break repair by the single-strand annealing (SSA) pathway. We found that among the pathogenic mutations in BRCA1, all were defective for DNA repair by either pathway. The HDR assay was accurate because all pathogenic mutants were defective for HDR, and all nonpathogenic variants were fully functional for HDR. Repair by SSA accurately identified pathogenic mutants, but several nonpathogenic variants were scored as defective or partially defective. These results indicated that specific amino acid residues of the BRCA1 protein have different effects in the two related DNA repair pathways, and these results validate the HDR assay as highly correlative with BRCA1-associated breast cancer.
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影响因子：
8
作者：
Kais, Z.;Chiba, N.;Ishioka, C.;Parvin, J. D.
通讯作者：
Parvin, J. D.
影响因子：
3.9
作者：
Millot, Gael A.;Carvalho, Marcelo A.;Caputo, Sandrine M.;Vreeswijk, Maaike P. G.;Brown, Melissa A.;Webb, Michelle;Rouleau, Etienne;Neuhausen, Susan L.;Hansen, Thomas V. O.;Galli, Alvaro;Brandao, Rita D.;Blok, Marinus J.;Velkova, Aneliya;Couch, Fergus J.;Monteiro, Alvaro N. A.
通讯作者：
Monteiro, Alvaro N. A.
DOI：
10.1126/science.1203430
发表时间：
2011-06-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cotta-Ramusino C;McDonald ER 3rd;Hurov K;Sowa ME;Harper JW;Elledge SJ
通讯作者：
Elledge SJ
影响因子：
9.8
作者：
Easton, Douglas F.;Deffenbaugh, Amie M.;Goldgar, David E.
通讯作者：
Goldgar, David E.
影响因子：
11.2
作者：
Judkins, T;Hendrickson, BC;Scholl, T
通讯作者：
Scholl, T