The Relationship Between Replication and Recombination

DNA replication, the process of copying double-stranded DNA, and DNA recombination, the process of breaking DNA strand and joined to a different strand, are central characteristics of life. The aim of this chapter is to discuss the relationship between replication and recombination. Understanding the intimate links between these processes gives us a more holistic approach to understanding the functioning of a cell. Replication and recombination machineries cooperate to maintain biological inheritance and genomic integrity. While replication enables the formation of two identical DNA molecules from a single double-stranded DNA, recombination enables accurate repair of errors that occur on both strands of DNA as well as the formation of new combinations of genes. Recombination can occur between similar molecules of DNA (homologous recombination), or dissimilar molecules (non-homologous end joining). Homologous recombination predominantly occurs during and shortly after DNA replication (late S and G2), while nonhomologous end joining is predominant in the G1 and early S phase of the cell cycle. What is the relationship between DNA replication and recombination processes? Mutations in some genes with a role in DNA replication cause hyper-recombination phenotypes. These mutations require recombination protein Rad52 for their viability, suggesting that the replication errors caused by mutations are repaired by recombination mechanisms (Merrill & Holm, 1998). Furthermore, many recombination genes have S phase defects when deleted. Obviously, replication and recombination processes are tightly intertwined. In this chapter I will try to present the close coupling between these processes from a different point of view (Fig. 1): recombination is part of DNA replication and, vice versa, DNA synthesis is part of the recombination process; both processes are connected via checkpoints; both processes are regulated by common posttranslational modifications; both processes take advantage of double helix DNA and both have a common problem with DNA unfolding. The recombination system plays a crucial role in DNA replication ensuring that replication machines can complete their task of genome duplication. DNA replication forks stall or collapse at DNA lesions or problematic genomic regions. When a fork becomes stalled, the replisome often remains firmly associated with the fork. But, when replication forks are removed, recombination is the most important rescue mechanism. The recombination mechanism forms substrates for the assembly of a new replication fork thus allowing continued DNA replication.