A hypothetical mechanism of noncanonical L1 DNA replication. A.Formation of an L1 DNA:RNA duplex. Heterogeneous FL-L1 RNAs, being assembledwith L1 ORF1p and ORF2p, find their “parental” complementarysequences in the genome and form L1 DNA:RNA hybrids. The chaperone activity ofORF1p, which includes the melting of mismatched duplexes, is deemedindispensable for pairing of the L1 RNA with the fully complementary L1 DNA.The displaced DNA strand of an L1 unit is likely stabilized by auxiliaryfactors. B. First-strand cDNA synthesis. ORF2p bound to the 3′ endof the FL-L1 RNA nicks the bottom DNA strand and synthesizes the first cDNAstrand from the liberated 3′-hydroxyl. C. Second nick formation.When ORF2p reaches the 5′ end of the L1 RNA, it nicks the top DNA strandat the 5′ end of the L1 element. ORF2p then switches templates from theRNA to the cDNA. The L1 RNA likely dissociates at this point. D.Second-strand cDNA synthesis on the first cDNA template. E. Nicking atthe genomic DNA-cDNA junctions and the ligation of the segments of the“parental” DNA at the sites of the first and second nicks byauxiliary factors. F. Unpairing of the new L1 cDNA strands and theirpairing with the “parental” strands by auxiliary factors. The endsof the new cDNA strands are joined with the new strands synthesized by thecanonical mechanism on the adjacent segments of the “parental”strands. Each cell division produces two cells with equal amounts of old andnew DNA synthesized by a combination of two different mechanisms.