Precise DNA replication depends on the S-phase checkpoint and PCNA dynamics. Research shows PAF15 acts as a "toolbelt" anchor, coordinating Okazaki fragment processing by preventing steric clashes between enzymes. ATR inhibition causes excessive origin firing, exhausting resources.

References:

• Chhetri G, Badugu S B, Petriman N A, et al. PAF15–PCNA exhaustion governs the strand-specific control of DNA replication[J]. Nature, 2026: 1-12.