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Dual-Incision and Repair Synthesis in NER

An additional level of coordination is likely achieved through a temporal coordination of the two dual-incision reactions. Studies using catalytically inactive versions of ERCC1 and XPG have shown that 5 -indsion by XPF requires the presence, but not catalytic activity of XPG [85, 86], while efficient 3 -indsion by XPG only occurs following 5 -indsion by XPF [71, 93], Furthermore, repair synthesis can be initiated in the presence of catalytically inactive XPG, providing another possible mechanism ensuring that exposure of persistent single-stranded DNA intermediates is actively prevented [93], [Pg.252]

Repair synthesis is executed by components of the replication machinery-the clamp loader RFC, the processivity factor PCNA, and the replicative Pols 8/e [51, 94], Recent studies have additionally implicated the translesion synthesis Pol k in repair synthesis [95], but what role the different polymerases play in the process remains to be elucidated. Following the fill-in reaction, the nick in the DNA is sealed by XRCC1-DNA ligase 3a in all stages of the cell cyde and by DNA ligase 1 in proliferating cells [96], thus completing the NER process. [Pg.252]


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