Holliday Junction Resolvases

Abstract

Four-way DNA intermediates, called Holliday junctions (HJs), can form during meiotic and mitotic recombination, and their removal is crucial for chromosome segregation. A group of ubiquitous and highly specialized structure-selective endonucleases catalyze the cleavage of HJs into two disconnected DNA duplexes in a reaction called HJ resolution. These enzymes, called HJ resolvases, have been identified in bacteria and their bacteriophages, archaea, and eukaryotes. In this review, we discuss fundamental aspects of the HJ structure and their interaction with junction-resolving enzymes. This is followed by a brief discussion of the eubacterial RuvABC enzymes, which provide the paradigm for HJ resolvases in other organisms. Finally, we review the biochemical and structural properties of some well-characterized resolvases from archaea, bacteriophage, and eukaryotes.

Regulation of Recombination and Genomic Maintenance

“…Although chromosome condensation may provide an intuitive barrier to HR, in turn, HR has been shown to affect chromosome condensation. Human cells with defects in processing HR-dependent joint molecules (e.g., BLM-deficient cells with con-current depletion of structure-selective endonucleases) show defects in chromosome condensation (Wechsler et al 2011;Wyatt and West 2014). It is unclear presently which mechanisms are at work, but one would suspect the three classes of SMC protein complexes to be involved (cohesins, condensins, and the Smc5/ Smc6 complex).…”

“…1). Cells of the human osteosarcoma cell line U2OS maintain their telomeres by ALT, and in these cells the MUS81 gene, encoding the catalytic subunit of MUS81-EME1 structure-selective endonuclease (see Wyatt and West 2014), becomes essential for growth (Zeng et al 2009). This may indicate a role of MUS81-EME1 in ALT directly, but could also be related to replication problems associated with the larger telomeres often found associated with ALT (Bryan et al 1995).…”

A new class of ultrafine anaphase bridges generated by homologous recombination

“…Breaks are repaired by DNA end resection followed by invasion of the resulting 3ʹ-single-stranded DNA (ssDNA) tail into the homologous sister chromatid to form a D-loop structure, which then serves as an initiation site for subsequent DNA synthesis [24]. HR often leads to the formation of DNA joint molecules in which the two recombining DNAs are covalently connected by a four-way DNA junction or Holliday junction (HJ) [25–27]. These intermediates can result in chromosome segregation defects if they are not processed before anaphase onset [28–32].…”

“…single HJs and D-loop structures), are processed by a second mechanism which involves structure-selective endonuclease (SSE)-mediated resolution [31,32,39,40]. There are two genetically distinct resolution pathways: one is mediated by the SLX1–SLX4, MUS81-EME1 and XPF-ERCC1 (SMX) tri-nuclease complex [27,31,41–46], and the other is mediated by GEN1 endonuclease [47–50]. …”

TopBP1-mediated DNA processing during mitosis

“…To avoid this scenario, joint molecule resolution by Holliday junction resolvases is upregulated during mitosis by several means (reviewed in refs. 69,70 ). Firstly, the EME1 subunit of the structure-selective endonuclease MUS81-EME1 is phosphorylated by CDK1 in mitosis 71 and this promotes the interaction to another structure-selective endonuclease SLX1-SLX4.…”