<P> Further research implicates the supplementary role of proliferating cell nuclear antigen (PCNA) to DNA ligase I's function of joining Okazaki fragments . When the PCNA binding site on DNA ligase I is inactive, DNA ligase I's ability to connect Okazaki fragments is severely impaired . Thus, a proposed mechanism follows: after a PCNA - DNA polymerase δ complex synthesizes Okazaki fragments, the DNA polymerase δ is released . Then, DNA ligase I binds to the PCNA, which is clamped to the nicks of the lagging strand, and catalyzes the formation of phosphodiester bonds . </P> <P> Flap endonuclease 1 (FEN1) is responsible for processing Okazaki fragments . It works with DNA polymerase to remove the RNA primer of an Okazaki fragment and can remove the 5' ribonucleotide and 5' flaps when DNA polymerase displaces the strands during lagging strand synthesis . The removal of these flaps involves a process called nick translation and creates a nick for ligation . Thus, FEN1's function is necessary to Okazaki fragment maturation in forming a long continuous DNA strand . Likewise, during DNA base repair, the damaged nucleotide is displaced into a flap and subsequently removed by FEN1 . </P> <P> In the presence of a single stranded DNA - binding protein RPA, the DNA 5' flaps become too long, and the nicks no longer fit as substrate for FEN1 . This prevents the FEN1 from removing the 5 ′ - flaps . Thus, Dna2's role is to reduce the 3 ′ end of these fragments, making it possible for FEN1 to cut the flaps, and the Okazaki fragment maturation more efficient . </P> <P> Although synthesis of the lagging strand involves only half the DNA in the nucleus, the complexity associated with processing Okazaki fragments is about twice that required to synthesize the leading strand . Even in small species such as yeast, Okazaki fragment maturation happens approximately a million times during a single round of DNA replication . Processing of Okazaki fragments is therefore very common and crucial for DNA replication and cell proliferation . </P>

What determines the size of okazaki fragments synthesized by e. coli dna polymerase iii (pol iii)