<P> There are two pathways that have been proposed to process Okazaki fragments . In the first pathway, only the nuclease FEN1 is involved . FEN1 cleaves the short "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases are prevented from binding to their complementary base pair--despite any base pairing downstream) immediately when they form . While this pathway can process basically all flaps, an issue with this pathway is that some flaps may escape cleavage and thus become long . These flaps then bind to replication protein A (RPA) which inhibits FEN1 cleavage . The second pathway thus becomes involved and is able to utilize both FEN1 and Dna2 nucleases to process the long flaps . Dna2 can cleave the RPA bound flap as it is able to displace to RPA, while creating a flap to which RPA cannot bind . Then, FEN1 will complete the cleavage of the flap . Dna2 is a key part of this process . Without the Dna2, the RPA bound flaps could not be processed which would ultimately lead to cell instability . The Pif1 helicase is also involved in this pathway as it aids creation of long flaps . Without the Pif1 helicase, the flaps would not become long enough to need cleavage by Dna2 . Recently, it has been suggested that an alternative pathway for Okazaki fragment processing exists . This alternative pathway occurs when the Pif1 helicase removes entire Okazaki fragments initiated by fold back flaps . </P> <P> Until recently, there were only two known pathways to process Okazaki fragments . However, current investigations have concluded that a new pathway for Okazaki fragmentation and DNA replication exists . This alternate pathway involves the enzymes Pol δ with Pif1 which perform the same flap removal process as Polδ and FEN1 . </P> <P> Primase adds RNA primers onto the lagging strand, which allows synthesis of Okazaki fragments from 5' to 3' . However, primase creates RNA primers at a much lower rate than that at which DNA polymerase synthesizes DNA on the leading strand . DNA polymerase on the lagging strand also has to be continually recycled to construct Okazaki fragments following RNA primers . This makes the speed of lagging strand synthesis much lower than that of the leading strand . To solve this, primase acts as a temporary stop signal, briefly halting the progression of the replication fork during DNA replication . This molecular process prevents the leading strand from overtaking the lagging strand . </P> <P> Following creation of RNA primers by primase on the lagging strand, DNA polymerase δ synthesizes Okazaki fragments . DNA polymerase δ also carries out a 3' to 5' exonuclease role, proofreading newly synthesized DNA strands during DNA replication . When the polymerase encounters an erroneous base pair, it removes one of the nucleotides and replaces it with a correct one . A third function of DNA polymerase δ is to supplement FEN1 / RAD27 5' Flap Endonuclease activity . This includes preventing and removing the strand displacement of 5' flaps, and creating ligatable nicks at the border of Okazaki fragments . </P>

Which enzyme seals okazaki fragments on the lagging strand