Cytosine residues in single-stranded DNA (ssDNA-C) (ssDNA-C)

Cytosine residues in single-stranded DNA (ssDNA) are critical molecular sites for both natural biological regulation and therapeutic targeting. These residues are uniquely susceptible to chemical and enzymatic modifications when DNA is in its single-stranded form, such as during replication, transcription, or viral infection [1]. The APOBEC family of enzymes targets these cytosines for deamination to uracil, a process vital for innate immunity against retroviruses but also a major source of mutational signatures in human cancers [2]. Furthermore, cytosine is the central player in epigenetic signaling through its conversion to 5-methylcytosine by DNA methyltransferases, a process targeted by drugs like decitabine to treat myelodysplastic syndromes [3][4]. Recent advancements in genome engineering have also utilized these residues as targets for cytosine base editors (CBEs), which allow for the precise correction of point mutations by converting C to T without inducing double-strand breaks [5]. Consequently, ssDNA cytosines represent a fundamental target for modulating genetic information and cellular identity. The accessibility of these residues is often transient, making their targeting highly dependent on the cellular state and DNA metabolic processes. Therapeutic strategies focusing on these residues must balance the desired modification with the risk of widespread genomic instability.

Other names

Single-stranded DNA cytosinessDNA-CDeoxycytidine in ssDNACytosine in ssDNA

Drugs and enzymes interact with cytosine residues in ssDNA through mechanisms such as covalent incorporation (nucleoside analogs), enzymatic deamination (APOBEC/Base editors), or methylation (DNMTs) to alter genetic coding or epigenetic signaling.