Nascent DNA strand

The nascent DNA strand is the newly synthesized polynucleotide chain formed during DNA replication, serving as the complementary copy of the parental template strand (Source [1], [18]). It is synthesized by DNA polymerases in the 5' to 3' direction, involving continuous synthesis on the leading strand and discontinuous synthesis of Okazaki fragments on the lagging strand (Source [13], [18]). In pharmacology, the nascent DNA strand is a critical target for nucleoside and nucleotide analogs, which act as antimetabolites (Source [4], [7]). These drugs are incorporated into the growing nascent chain, where they function as chain terminators or induce structural distortions that stall replication forks (Source [1], [10]). Disruption of nascent DNA synthesis or maturation is a potent mechanism for inducing cell death in rapidly dividing cells, such as cancer cells and virally infected cells (Source [10], [14]). For instance, PARP inhibitors are known to impede the maturation of nascent DNA strands, leading to the accumulation of DNA breaks and synthetic lethality in homologous recombination-deficient tumors (Source [2], [3]). Protective proteins like BRCA1, BRCA2, and WRN are essential for maintaining the integrity of nascent DNA under conditions of replication stress (Source [8], [11]). Consequently, the nascent DNA strand is not only a direct target for cytotoxic agents but also a focal point for precision therapies that exploit defects in DNA repair and replication pathways (Source [14], [15]).

Other names

Newly synthesized DNADaughter DNA strandNascent DNAOkazaki fragments

Incorporation of nucleoside analogs into the nascent strand leads to chain termination or replication fork stalling; inhibitors of repair enzymes like PARP impede the maturation and ligation of nascent DNA fragments (Source [1], [2], [4]).