SLX4 interacts with RTEL1 to prevent transcription-mediated DNA replication perturbations.

The SLX4 tumor suppressor is a scaffold that plays a pivotal role in several aspects of genome protection, including homologous recombination, interstrand DNA crosslink repair and the maintenance of common fragile sites and telomeres. Here, we unravel an unexpected direct interaction between SLX4 and the DNA helicase RTEL1, which, until now, were viewed as having independent and antagonistic functions. We identify cancer and Hoyeraal-Hreidarsson syndrome-associated mutations in SLX4 and RTEL1, respectively, that abolish SLX4-RTEL1 complex formation. We show that both proteins are recruited to nascent DNA, tightly co-localize with active RNA pol II, and that SLX4, in complex with RTEL1, promotes FANCD2/RNA pol II co-localization. Importantly, disrupting the SLX4-RTEL1 interaction leads to DNA replication defects in unstressed cells, which are rescued by inhibiting transcription. Our data demonstrate that SLX4 and RTEL1 interact to prevent replication-transcription conflicts and provide evidence that this is independent of the nuclease scaffold function of SLX4.

[Ultrasonic geometry of synthetic endoprostheses after transabdominal preperitoneal hernioplasty of inguinal hernias]. / Ul'trazvukovaia geometriia sinteticheskikh éndoprotezov posle transabdominal'noi preperitoneal'noi gernioplastiki pakhovoi gryzhi.

OBJECTIVE: To assess position of mesh endoprosthesis in retroperitoneal space after TARR hernioplasty using ultrasound in early and long-term postoperative period. MATERIAL AND METHODS: There were 30 patients with inguinal hernias after TARR procedure. Standard technology of laparoscopic transabdominal preperitoneal hernioplasty was used in all patients. In all cases, a large-pore monofilament polypropylene mesh 10x15 cm was used. Control examination and ultrasound of the mesh implant were performed the next day, in 1, 3, 6, 12 months after surgery. Correct position of the implant was determined by its placement at the level of pubic bone with complete overlap of posterior wall of the inguinal canal and inner ring. RESULTS: US-image of the implant is present in two geometric forms - linear and sinusoid. The shape of prosthesis varies depending on postoperative period and the use of fixing elements. Thus, sinusoidal shape of prosthesis was observed in patients without fixation of prosthesis the next day and in 1 month after TARR. Geometry of the implant acquired the form of a straight line after 3 months and became almost a straight line in 12 months after surgery. Linear shape of prosthesis in early postoperative period was found after intraoperative fixation of endoprosthesis. Sinusoidal shape is noted after 3 months. Ultrasonic pattern of endoprosthesis looked as a thin hyperechoic band with thickness of 1.2-3.9 mm. Mean thickness of prosthesis was 2.2±0.1 mm the next day after surgery, 2.8±0.2 mm after 1 month and 1.6±0.05 mm after 12 months. CONCLUSION: Geometry of synthetic implants after TARR hernioplasty undergoes significant changes and depends on duration of postoperative period and fixation of the prosthesis.

In search of candidate genes critically expressed in the human endometrium during the window of implantation.

BACKGROUND: In this prospective randomized blinded clinical trial, we examined gene expression profiles of the human endometrium during the early and mid-luteal phases of the natural cycle. METHODS: An endometrial biopsy was performed on day 16 (LH +3) or on day 21 (LH +8), followed by RNA extraction and microarray analysis using an Affymetrix HG-U95A microchip. Data analysis was carried out using pairwise multiple group comparison with the significance analysis of microarrays (SAM) software. RESULTS: With a false discovery rate of 0, the analysis revealed that 107 genes were significantly and differently expressed (> or =2-fold) during the early versus the mid-luteal phase of the cycle. Forty-five of these genes have not been previously linked to endometrial receptivity. Validation of the microarray data was accomplished using semiquantitative RT-PCR. We demonstrated the presence of estrogen and progesterone response elements (ERE and PRE) by analysis of the 5'-flanking regions of a subset of differentially regulated genes. CONCLUSIONS: Using a strict bioinformatics approach of microarray data, we demonstrated significant changes in candidate genes during the transition of the early to the mid-luteal phase of the human endometrium that may have functional significance for the opening and maintenance of the window of implantation.