title: Resolution of Recombination Intermediates: Mechanisms and Regulation.
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.
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: West
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Miguel G
authors.initials: MG
authors.lastname: Blanco
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Ying Wai
authors.initials: YW
authors.lastname: Chan
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Joao
authors.initials: J
authors.lastname: Matos
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Shriparna
authors.initials: S
authors.lastname: Sarbajna
authors.affiliation: The Francis Crick Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, United Kingdom.
authors.forename: Haley D M
authors.initials: HD
authors.lastname: Wyatt
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D045566:DNA, Cruciform / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D045565:Holliday Junction Resolvases / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D009687:Nuclear Proteins / Q000378:metabolism; D053484:RecQ Helicases / Q000378:metabolism; D045522:Recombinases / Q000378:metabolism; D059767:Recombinational DNA Repair; D012854:Sister Chromatid Exchange
chemical_list: D002352:Carrier Proteins; D045566:DNA, Cruciform; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501527:RMI1 protein, human; C533196:RMI2 protein, human; D045522:Recombinases; C507947:Eme1 protein, human; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C498772:MUS81 protein, human; C542320:SLX1 protein, human; C542319:SLX4 protein, human; C533748:GEN1 protein, human; D045565:Holliday Junction Resolvases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; D004264:DNA Topoisomerases, Type I