Synergy Between DNA Replication and Repair Mechanisms

Abstract

DNA replication is a fundamental and stringently regulated cellular process that ensures the accurate propagation of the cell’s genetic material. An accurate duplication of the genome and segregation to the daughter cells is essential, as any unreplicated genomic regions will result in breaks and deletions during mitosis, including regions containing tumor suppressor genes, while local DNA over-replication will result in gene, and possibly oncogene, amplification (Gonzalez et al., 2005). Several DNA replication proteins, both initiator and replication fork (reviewed in (Hubscher, 2009)) proteins, have been shown to also play an essential role in several DNA repair pathways, such as base excision repair, nucleotide excision repair, and double-strand (ds) break and mismatch repair. Recent work from prokaryotes and eukaryotes has indicated that replication initiator proteins are also directly involved in multiple cellular processes (reviewed in (Scholefield et al., 2011)), coordinating the initiation of DNA replication with other cell cycle-related activities, including DNA repair (Moldovan et al., 2007; Oakley and Patrick, 2010). DNA repair, like all major cellular functions, including transcription and DNA replication, is a tightly regulated process. This review deals with the apparent synergy between the DNA replication and repair mechanisms.