Repriming DNA synthesis: an intrinsic restart pathway that maintains efficient genome replication

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Cells employ DNA damage tolerance (DDT) mechanisms like translesion synthesis and fork reversal to overcome replication impediments.
• Lagging strand synthesis involves Okazaki fragments, with post-replication gap filling.
• The continuity of leading strand synthesis has been a long-standing debate in DNA replication.

Observation:

• Early research suggested discontinuous synthesis for both DNA strands.
• Later studies favored a semi-discontinuous replication model with continuous leading strand synthesis.
• Recent findings confirm leading strand repriming by replicative primases in prokaryotes.

Findings:

• Eukaryotes utilize PrimPol, a specialized primase, for leading strand repriming downstream of lesions.
• PrimPol facilitates fork restart and maintains efficient replication fork progression.
• Repriming is now recognized as an intrinsic pathway for replication restart in prokaryotes and eukaryotes.

Implications:

• This review consolidates evidence supporting repriming as a universal mechanism for genome duplication.
• Understanding repriming is crucial for comprehending DNA replication fidelity and stability.
• The findings highlight the conserved nature of essential DNA replication processes across all domains of life.