Resolution of Recombination Intermediates: Mechanisms and Regulation (original) (raw)

Miguel G. Blanco 1,
Ying Wai Chan,
Joao Matos 2,
Shriparna Sarbajna 3 and
Haley D.M. Wyatt
The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom
Correspondence: stephen.west{at}crick.ac.uk

↵1 Present address: Department of Biochemistry and Molecular Biology, CIMUS, University of Santiago de Compostela, 15706 Santiago de Compostela, Spain.
↵2 Present address: Institute of Biochemistry, ETH Zurich, Zurich 8093, Switzerland.
↵3 Present address: Adelphi Values, Adelphi Mill, Bollington, Cheshire SK10 5JB, United Kingdom.

Abstract

DNA strand break repair by homologous recombination leads to the formation of intermediates in which sister chromatids are covalently linked. The efficient processing of these joint molecules, which often contain four-way structures known as Holliday junctions, is necessary for efficient chromosome segregation during mitotic division. Because persistent chromosome bridges pose a threat to genome stability, cells ensure the complete elimination of joint molecules through three independent pathways. These involve (1) BLM-Topoisomerase IIIα-RMI1-RMI2 (BTR complex), (2) SLX1-SLX4-MUS81-EME1 (SLX-MUS complex), and (3) GEN1. The BTR pathway promotes the dissolution of double Holliday junctions, which avoids the formation of crossover products, prevents sister chromatid exchanges, and limits the potential for loss of heterozygosity. In contrast to BTR, the other two pathways resolve Holliday junctions by nucleolytic cleavage to yield crossover and non-crossover products. To avoid competition with BTR, the resolution pathways are restrained until the late stages of the cell cycle. The temporal regulation of the dissolution/resolution pathways is therefore critical for crossover avoidance while also ensuring that all covalent links between chromosomes are resolved before chromosome segregation.