Journal
TRENDS IN BIOCHEMICAL SCIENCES
Volume 39, Issue 9, Pages 409-419Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tibs.2014.07.003
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Funding
- Cancer Research UK
- European Research Council
- Louis-Jeantet Foundation
- Cancer Research UK [11582] Funding Source: researchfish
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Holliday junctions (HJs) are four-stranded DNA intermediates that arise during the recombinational repair of DNA double-strand breaks (DSBs). Their timely removal is crucial for faithful chromosome segregation and genome stability. In mammalian cells, HJs are processed by the BTR (BLM-topoisomerase Ill alpha-RMI1-RMI2) complex, the SLX-MUS (SLX1-SLX4-MUS81-EME1) complex, and the GEN1 resolvase. Recent studies have linked the deficiency of one or more of these enzymes to perturbed DNA replication, impaired crosslink repair, chromosomal instability, and defective mitoses, coupled with the transmission of widespread DNA damage and high levels of mortality. We review these key advances and how they have cemented the status of HJ-processing enzymes as guardians of genome integrity and viability in mammalian cells.
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