AI Article Synopsis
- Human APOBEC3 enzymes modify single-stranded DNA, with five targeting mitochondrial DNA and three targeting viral DNA, but only APOBEC3A causes significant changes to genomic DNA.
- In studies of APOBEC3A isoforms p1 and p2, both were found to migrate to the nucleus and lead to hypermutation of CMYC DNA, resulting in DNA double strand breaks and triggering cell cycle arrest and apoptosis.
- The activation of CD4+ T lymphocytes suggested that APOBEC3A could contribute to DNA mutations in inflammatory conditions, possibly linking it to the genomic changes seen in various cancers due to chronic inflammation.
Article Abstract
Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed the distribution and function of the two APOBEC3A isoforms p1 and p2 in transfected cell lines. Both can translocate to the nucleus and hypermutate CMYC DNA and induce DNA double strand breaks as visualized by the detection of ©H2AX or Chk2. APOBEC3A induced G1 phase cell cycle arrest and triggered several members of the intrinsic apoptosis pathway. Activation of purified human CD4+ T lymphocytes with PHA, IL2 and interferon α resulted in C->T hypermutation of genomic DNA and double stranded breaks suggesting a role for APOBEC3A in pro-inflammatory conditions. As chronic inflammation underlies many diseases including numerous cancers, it is possible that APOBEC3A induction may generate many of the lesions typical of a cancer genome.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748023 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073641 | PLOS |
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