Ultrasonographic evaluation of abnormal uterine bleeding in postmenopausal women

Background: Objectives of current study were to diagnose causes of Abnormal Uterine Bleeding (AUB) in postmenopausal women (PMW) and to correlate it with curettage and histopathological findings, hysteroscopy and thereby minimizing unnecessary interventions in the form of operations and hysteroscopy where sonography depicts normal findings.Methods: After obtaining ethical clearance present prospective observational study was conducted from November 2010 to November 2012, to evaluate the endometrium in 50 postmenopausal women (PMW) with bleeding per vagina referred to the department of Radio diagnosis by the department of gynaecology in Bangalore medical college and research institute. After applying inclusion and exclusion criterias the cases were evaluated with ultrasonography both transabdominal (TAS) and transvaginal scan (TVS where ever necessary). Histopathological and hysteroscopic correlation was done in all cases.Results: 58% of the PMW with bleed were in the age group of 51-60 years. Most common cause of PMB was atrophic endometrium (44%), endometrial polyp (22%), followed by malignancy (14%), and hyperplastic endometrium (6%). At Endometrium thickness less than 4 mm there were nil chances of carcinoma.Conclusions: In women with AUB in postmenopausal age ultrasonography (USG) can be considered as an initial imaging modality for diagnosing endometrial diseases. The sensitivity and specificity of USG for Atrophic endometrium is 100% & 84% respectively with accuracy of 100%, endometrial polyp the specificity is 100% with accuracy of 88%. For malignancy USG showed 100% specificity & accuracy of 100%. Hence USG is highly accurate for evaluating endometrial pathologies. Being noninvasive, less costly & good patient compliance USG should be considered as an initial imaging modality over invasive investigations like D&C, hysteroscopy in evaluating endometrial disorders

A protective role for BRCA2 at stalled replication forks

The hereditary breast and ovarian cancer predisposition genes BRCA1 and BRCA2 account for the lion's share of heritable breast cancer risk in the human population. Loss of function of either gene results in defective homologous recombination (HR) and triggers genomic instability, accelerating breast tumorigenesis. A long-standing hypothesis proposes that BRCA1 and BRCA2 mediate HR following attempted replication across damaged DNA, ensuring error-free processing of the stalled replication fork. A recent paper describes a new replication fork protective function of BRCA2, which appears to collaborate with its HR function to suppress genomic instability

Molecular basis of microhomology-mediated end-joining by purified full-length Polθ

DNA polymerase θ (Polθ) is a unique polymerase-helicase fusion protein that promotes microhomology-mediated end-joining (MMEJ) of DNA double-strand breaks (DSBs). How full-length human Polθ performs MMEJ at the molecular level remains unknown. Using a biochemical approach, we find that the helicase is essential for Polθ MMEJ of long ssDNA overhangs which model resected DSBs. Remarkably, Polθ MMEJ of ssDNA overhangs requires polymerase-helicase attachment, but not the disordered central domain, and occurs independently of helicase ATPase activity. Using single-particle microscopy and biophysical methods, we find that polymerase-helicase attachment promotes multimeric gel-like Polθ complexes that facilitate DNA accumulation, DNA synapsis, and MMEJ. We further find that the central domain regulates Polθ multimerization and governs its DNA substrate requirements for MMEJ. These studies identify unexpected functions for the helicase and central domain and demonstrate the importance of polymerase-helicase tethering in MMEJ and the structural organization of Polθ

Publisher Correction: Molecular basis of microhomology-mediated end-joining by purified full-length Polθ (Nature Communications, (2019), 10, 1, (4423), 10.1038/s41467-019-12272-9)

The original version of this Article contained errors in Figure 6. In panel o, the labels incorrectly stated ‘Poleθ’ and “Poleθ + DNA” and should be labelled “Polθ” and “Polθ + DNA”. In the result section, in the sub-section entitled “Polθ Promotes MMEJ of Long ssDNA”, the sentence “Importantly, the ability of Polθ- pol to perform MMEJ on short (≤12 nt) ssDNA (Fig. 1p, left; Supplementary Fig. 3D and 3E), and short (≤15 nt) overhangs, demonstrates it performs interstrand pairing without Polθ-hel”. should read as follow: “Importantly, the ability of Polθ-pol to perform MMEJ on short (≤12 nt) ssDNA (Fig. 1p, left; Supplementary Fig. 3D and 3E), and short (≤15 nt) overhangs, demonstrates that it performs interstrand pairing without Polθ-hel”. In the sub-section entitled “Preventing Intrastrand Pairing Stimulates MMEJ by Polθ-Pol”, the sentence “We predicted that preventing base-pairing opportunities between 3' terminal bases and bases upstream along long the 5' region of long ssDNA substrates would suppress intrastrand pairing and enable interstrand pairing by Polθ-pol (Fig. 3c)”. should read as follows: “We predicted that preventing base-pairing opportunities between 3' terminal bases and bases upstream along the 5' region of long ssDNA substrates would suppress intrastrand pairing and enable interstrand pairing by Polθ-pol (Fig. 3c)”. In the method section, in the “Proteins” sub-section the sentence “Polθ-pol, Polθ-hel and RPA were purified as described”. should read as follows: “Polθ-pol and Polθ-hel were purified as described”. These corrections have now been included in the HTML and pdf of the article. Additionally, a technical problem during the publication process resulted in loss of image quality in Figs. 1, 3 and 4. This has now been corrected in both the PDF and HTML versions of the Article