Indeed, loss of Sgs1 or BLM activity results in increased mitotic COs and may explain the high levels of SCEs in BS cells. The double depletion of him-6 and top-3 alpha genes in C. elegans led to a massive increase in DSBs and chromosomal abnormalities in germ cells. In addition, over-expressed TOP-3 alpha and HIM-6 proteins showed specific physical interactions in vitro. Based on these genetic and biochemical data, HIM-6 is predicted to participate in the dissolution of dHJs. Our observation that HIM-6 unwound a single HJ may indicate that it is also capable of partially unwinding dHJs. However, to determine whether these in vitro HIM-6 activities may promote NCOs at the expense of COs in vivo, the TOP-3 alpha and HIM-6 complex needs to be further characterized. In addition, a recent study showed that him-6 mutations in combination with mutations in the structure-specific nucleases, mus-81 and slx-1, produce mitotic defects, including embryonic lethality and larval arrest, and suggest an in vivo role for him-6 in processing recombination intermediates. In meiotic recombination, HJs including dHJs can be formed between homologous chromosomes and are initiated by the introduction of programmed DSBs. In yeast, it was been shown that NCOs are formed in an Sgs1-dependent manner. Recently, In C. elegans, an important role for HIM-6 in meiotic recombination was reported. Worms with him-6 and mus-81 mutations exhibited increased recombination intermediates, suggesting that HIM-6 and MUS-81 may limit early production of recombination intermediates in meiosis. In addition, worms with mutations in him-6 and xpf-1, an endonuclease related to MUS-81, displayed pairs of univalents linked by chromatin bridges representing unresolved meiotic HJs and reduced CO recombination. These data suggest that HIM-6 and XPF-1 may promote HJ resolution and processing of meiotic recombination intermediates WY 14643 50892-23-4 leading to CO products. However, exactly how HIM-6 acts with these nucleases remains unclear. Our observations indicated that HIM-6 was able to unwind HJs and D-loops, therefore it is reasonable to speculate that HIM-6 functions to target and/or activate these nucleases at an HJ or a D-loop. Further biochemical studies with HIM-6 and these nucleases will help uncover these roles of HIM-6. Moreover, co-localization with other proteins involved in meiotic recombination, such as XPF-1 and SLX-4, remains to be investigated. When a replication fork is stalled at a DNA lesion on the leading strand, an HJ can be formed through regression of the nascent leading and lagging strands. This type of HJ can be resolved by repair or bypassed. A recent in vivo study showed that human RecQ helicases, WRN and BLM, function in the reactivation of forks after treatment with HU. In addition, BLM localized to repair centers at collapsed replication forks in response to HU. Biochemical studies showed that BLM regresses the stalled replication fork and separates HJ structures. Although in vivo data on the reactivation of forks after HU treatment are not currently available in C. elegans him-6 mutants our observation.