Jun Nakamura1, Mai Nakamura2. 1. Laboratory of Laboratory Animal Science, Graduate School of Life and Environmental Biosciences, Osaka Prefecture University, Izumisano, Osaka, Japan. Electronic address: junnakamura77777@gmail.com. 2. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract
Covalent binding between proteins and a DNA strand produces DNA-protein crosslinks (DPC). DPC are one of the most deleterious types of DNA damage, leading to the blockage of DNA replication and transcription. Both DNA lesions and endogenous products with carbonyl functional groups can produce DPC in genomic DNA under normal physiological conditions. For example, formaldehyde, the most abundant endogenous human carcinogen, and apurinic/apyrimidinic (AP) sites, the most common type of endogenous DNA lesions, has been shown to crosslink proteins and/or DNA through their carbonyl functional groups. Unfortunately, compared to other types of DNA damage, DPC have been less studied and understood. However, a recent advancement has allowed researchers to determine accurate yields of various DNA lesions including formaldehyde-derived DPC with high sensitivity and specificity, paving the way for new developments in this field of research. Here, we review the current literature and remaining unanswered questions on DPC formation by endogenous formaldehyde and various aldehydic 2-deoxyribose lesions.
Covalent binding between proteins and a DNan class="Gene">A strne">and produces DNan class="Gene">A-protein crosslinks (DPC). DPC are one of the most deleterious types of DNAdamage, leading to the blockage of DNA replication and transcription. Both DNA lesions and endogenous products with carbonyl functional groups can produce DPC in genomic DNA under normal physiological conditions. For example, formaldehyde, the most abundant endogenous human carcinogen, and apurinic/apyrimidinic (AP) sites, the most common type of endogenous DNA lesions, has been shown to crosslink proteins and/or DNA through their carbonyl functional groups. Unfortunately, compared to other types of DNAdamage, DPC have been less studied and understood. However, a recent advancement has allowed researchers to determine accurate yields of various DNA lesions including formaldehyde-derived DPC with high sensitivity and specificity, paving the way for new developments in this field of research. Here, we review the current literature and remaining unanswered questions on DPC formation by endogenous formaldehyde and various aldehydic 2-deoxyribose lesions.
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