Abstract
Homologous recombination is essential for DNA repair, replication and the exchange of genetic material between parental chromosomes during meiosis. The stages of recombination involve complex reorganization of DNA structures, and the successful completion of these steps is dependent on the activities of multiple helicase enzymes. Helicases of many different families coordinate the processing of broken DNA ends, and the subsequent formation and disassembly of the recombination intermediates that are necessary for template-based DNA repair. Loss of recombination-associated helicase activities can therefore lead to genomic instability, cell death and increased risk of tumor formation. The efficiency of recombination is also influenced by the ‘anti-recombinase’ effect of certain helicases, which can direct DNA breaks toward repair by other pathways. Other helicases regulate the crossover versus non-crossover outcomes of repair. The use of recombination is increased when replication forks and the transcription machinery collide, or encounter lesions in the DNA template. Successful completion of recombination in these situations is also regulated by helicases, allowing normal cell growth, and the maintenance of genomic integrity.
Highlights
Homologous recombination (HR) is an essential cellular process, which is required to repair DNA double strand breaks (DSBs), restart collapsed replication forks, and for the rearrangement of genetic information from parental chromosomes during meiosis [1]
As discussed above, Bloom Syndrome helicase (BLM) helicase has been reported to function in DNA end resection, Two helicases of the Fanconi Anemia gene family, FANCJ and FANCM, are important for fork stability
Mph1, the yeast homolog of FANCM, can reverse replication forks, and this activity is regulated in part by the SMC5-6 complex [134,135,136]
Summary
Homologous recombination (HR) is an essential cellular process, which is required to repair DNA double strand breaks (DSBs), restart collapsed replication forks, and for the rearrangement of genetic information from parental chromosomes during meiosis [1]. Helicases have been shown to be necessary to carry out various steps of recombination, and for regulation of the rate and outcomes of recombination (Table 1). Several of these proteins are classical helicases, which act to unwind single-stranded DNA, whereas others can be classed as translocases, which use their motor activity to move along double-stranded DNA regions [2]. Recombination proceeds by resection of DNA ends to form a single-stranded region, which is initially bound by Replication Protein A (RPA), and subsequently by RAD51 [1,3]. Promotes End Resection, RAD51 Displacement, D-Loop Disruption, Holliday Junction Migration and Dissolution. Understanding the contribution of helicases to recombination is essential to identify how these proteins enable normal growth of the cell
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