XPF mediates 3' flap processing for FEN1-independent Okazaki fragment maturation.

ABSTRACT: Okazaki fragment maturation (OFM), the process that removes RNA-DNA primers, is a major source of DNA replication stress and mutations. It involves Polδ-mediated DNA strand displacement synthesis that produces 5' flaps, FEN1-mediated 5' flap cleavage, and LIG1-catalyzed nick ligation. Recently, we discovered that under stress conditions, yeast cells convert 5' flaps into 3' flaps, which are degraded by 3' flap nucleases to produce ligatable DNA nicks. However, little is known about this stress-induced, 3' flap-based OFM in human cells. Here, we report that 3' flaps frequently form in various human cancer cells, and that FEN1 deficiency significantly enhances 3' flap levels. XPF1 is recruited to the replication forks in FEN1 mutant or FEN1-chemically inhibited cells. Notably, XPF deficiency

SUBMITTER: Li K 

PROVIDER: S-EPMC12633238 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature