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Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

ABSTRACT: Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartments. Here, we map a DNA-binding interface to the S compartment of E heads SmcScpAB and show that head-DNA association is essential for efficient DNA translocation and for traversing highly transcribed genes in Bacillus subtilis. We demonstrate that in J heads, SmcScpAB chromosomal DNA resides in the K compartment but is absent from the S compartment. Our results imply that the DNA occupancy of the S compartment changes during the ATP hydrolysis cycle. We propose that DNA translocation involves DNA entry into and exit out of the S compartment, possibly by DNA transfer between compartments and DNA segment capture.

SUBMITTER: Vazquez Nunez R

PROVIDER: S-EPMC6934413 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

Vazquez Nunez Roberto R Ruiz Avila Laura B LB Gruber Stephan S

Molecular cell 20190611 2

Multi-subunit SMC ATPases control chromosome superstructure and DNA topology, presumably by DNA translocation and loop extrusion. Chromosomal DNA is entrapped within the tripartite SMCkleisin ring. Juxtaposed SMC heads ("J heads") or engaged SMC heads ("E heads") split the SMCkleisin ring into "S" and "K" sub-compartments. Here, we map a DNA-binding interface to the S compartment of E heads SmcScpAB and show that head-DNA association is essential for efficient DNA translocation and for traversin ...[more]

PMID: 31201090

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Project description:Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We used the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN to analyze NCAPD2 expression and promoter methylation levels in 33 tumors and normal samples. We performed immunohistochemistry (IHC) on liver cancer and corresponding normal tissues to examine NCAPD2 protein expression in LIHC. Kaplan-Meier survival and univariate regression analyses were performed to explore the pan-cancer clinical significance of NCAPD2. Moreover, correlative analysis between NCAPD2 expression and clinical characteristics, immune cell infiltration, immune checkpoints, immune regulators, tumor mutation burden (TMB), microsatellite instability (MSI), ribonucleic acid (RNA) methylation regulators, and drug sensitivity was conducted using data from TCGA. We also investigated the effects of NCAPD2 expression on immunotherapy efficacy and prognosis. Gene set enrichment analysis (GSEA) was conducted using NCAPD2. Bioinformatic analysis showed that NCAPD2 was overexpressed in most tumors and correlated with the clinical characteristics of some cancers. IHC results demonstrated that NCAPD2 protein expression was higher in LIHC than in normal liver. NCAPD2 expression was linked with T stage, clinical stage, and histologic grade in LIHC. Overexpression of NCAPD2 resulted in poor overall survival, and disease-specific survival in adrenocortical carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, pancreatic adenocarcinoma, sarcoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma. NCAPD2 was considered an independent biomarker by Cox regression in LIHC. The time ROC curve demonstrated that the survival rate of 1-, 3-, and 5-year OS and DSS in LIHC was above 0.6. The expression of NCAPD2 was significantly correlated with immune cell infiltration, immune checkpoints, TMB, MSI, and RNA methylation regulators in several tumors. NCAPD2 had a high predictive value for immunotherapy efficiency in certain tumors. In our study, drugs sensitive to NCAPD2 protein were screened by sensitivity analysis. GSEA analysis showed that NCAPD2 mainly participated in the G2M checkpoint, mitotic spindle, and KRAS-signaling. NCAPD2 may act as a prognostic molecular marker in most cancers.

Dataset Information

Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

Publications

Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin.

Similar Datasets

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