Abstract 3366: APOBEC3 family of cytidine deaminases in sensitizing triple-negative breast cancer cells to cisplatin and carboplatin

Cisplatin is a DNA damaging chemotherapeutic which forms interstrand crosslinks (ICL) and intrastrand adducts that induce replication fork collapse and lead to apoptosis. These adduct sites can be repaired through several repair pathways, the most important being nucleotide excision repair (NER). Ci...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2018-07, Vol.78 (13_Supplement), p.3366-3366
Main Authors: Conner, Kayla L., Shaik, Asra N., White, Jordan, Lei, Wen, Cote, Michele L., Patrick, Steve M.
Format: Article
Language:English
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Summary:Cisplatin is a DNA damaging chemotherapeutic which forms interstrand crosslinks (ICL) and intrastrand adducts that induce replication fork collapse and lead to apoptosis. These adduct sites can be repaired through several repair pathways, the most important being nucleotide excision repair (NER). Cisplatin and carboplatin ICLs form a unique structure that forces cytosines flanking the adduct site to become extrahelical. Our lab has previously shown that base excision repair (BER) and mismatch repair (MMR) mediate sensitivity to cisplatin and carboplatin as a consequence of nonproductive processing of DNA flanking the ICL structure. The APOBEC3 (A3) protein family of cytidine deaminases have recently been implicated in cancer development and have potential to deaminate the extrahelical cytosines formed by cisplatin ICLs. PolĪ² knockdown MDA-MB-231 cells are resistant to cisplatin in vivo compared to wild-type cells (p
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2018-3366