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DNA脱氨酶诱导与断裂相关的突变簇，提示APOBEC3B和3A在乳腺癌kataegis中的作用。

DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis.

作者信息

Taylor Benjamin Jm, Nik-Zainal Serena, Wu Yee Ling, Stebbings Lucy A, Raine Keiran, Campbell Peter J, Rada Cristina, Stratton Michael R, Neuberger Michael S

机构信息

Protein and Nucleic Acid Chemistry Division , Medical Research Council Laboratory of Molecular Biology , Cambridge , United Kingdom.

出版信息

Elife. 2013 Apr 16;2:e00534. doi: 10.7554/eLife.00534.

DOI:10.7554/eLife.00534
PMID:23599896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3628087/
Abstract

Breast cancer genomes have revealed a novel form of mutation showers (kataegis) in which multiple same-strand substitutions at C:G pairs spaced one to several hundred nucleotides apart are clustered over kilobase-sized regions, often associated with sites of DNA rearrangement. We show kataegis can result from AID/APOBEC-catalysed cytidine deamination in the vicinity of DNA breaks, likely through action on single-stranded DNA exposed during resection. Cancer-like kataegis can be recapitulated by expression of AID/APOBEC family deaminases in yeast where it largely depends on uracil excision, which generates an abasic site for strand breakage. Localized kataegis can also be nucleated by an I-SceI-induced break. Genome-wide patterns of APOBEC3-catalyzed deamination in yeast reveal APOBEC3B and 3A as the deaminases whose mutational signatures are most similar to those of breast cancer kataegic mutations. Together with expression and functional assays, the results implicate APOBEC3B/A in breast cancer hypermutation and give insight into the mechanism of kataegis. DOI:http://dx.doi.org/10.7554/eLife.00534.001.

摘要

乳腺癌基因组揭示了一种新的突变簇形式（kataegis），其中在相距1至数百个核苷酸的C:G碱基对处的多个同链替换聚集在千碱基大小的区域上，通常与DNA重排位点相关。我们发现kataegis可能是由DNA断裂附近的AID/APOBEC催化的胞嘧啶脱氨作用导致的，可能是通过对切除过程中暴露的单链DNA起作用。在酵母中表达AID/APOBEC家族脱氨酶可重现类似癌症的kataegis，这在很大程度上依赖于尿嘧啶切除，尿嘧啶切除会产生一个无碱基位点用于链断裂。局部的kataegis也可由I-SceI诱导的断裂引发。酵母中APOBEC3催化脱氨作用的全基因组模式显示，APOBEC3B和3A是脱氨酶，其突变特征与乳腺癌kataegic突变最为相似。结合表达和功能分析，这些结果表明APOBEC3B/A与乳腺癌超突变有关，并深入了解了kataegis的机制。DOI:http://dx.doi.org/10.7554/eLife.00534.001 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/b2b1fb18378a/elife00534f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/1b6438c9dceb/elife00534f001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/1b6438c9dceb/elife00534f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/c027b4c9e35e/elife00534fs001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/2a0b1d79da6f/elife00534f002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c3e/3628087/e8e0218e7d3c/elife00534fs004.jpg
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PLoS Genet. 2012;8(12):e1003149. doi: 10.1371/journal.pgen.1003149. Epub 2012 Dec 13.
3
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Viruses. 2025 Apr 1;17(4):514. doi: 10.3390/v17040514.
4
Defining APOBEC-induced mutation signatures and modifying activities in yeast.定义酵母中APOBEC诱导的突变特征和修饰活性。
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5
Oligo-seq protocol for mapping DNA motifs targeted by base editors.用于绘制碱基编辑器靶向的DNA基序的寡核苷酸测序方案。
STAR Protoc. 2025 Apr 10;6(2):103758. doi: 10.1016/j.xpro.2025.103758.
6
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