Background: As part of our investigation into the genetic basis of tumor cell radioresponse, we have isolated several clones with a wide range of responses to X-radiation (XR) from an unirradiated human colorectal tumor cell line, HCT116. Using human cDNA microarrays, we recently identified a novel gene that was down-regulated by two-fold in an XR-resistant cell clone, HCT116Clone2_XRR. We have named this gene as X-ray radiation resistance associated 1 (XRRA1) (GenBank BK000541). Here, we present the first report on the molecular cloning, genomic characterization and over-expression of the XRRA1 gene.

Results: We found that XRRA1 was expressed predominantly in testis of both human and macaque. cDNA microarray analysis showed three-fold higher expression of XRRA1 in macaque testis relative to other tissues. We further cloned the macaque XRRA1 cDNA (GenBank AB072776) and a human XRRA1 splice variant from HCT116Clone2_XRR (GenBank AY163836). In silico analysis revealed the full-length human XRRA1, mouse, rat and bovine Xrra1 cDNAs. The XRRA1 gene comprises 11 exons and spans 64 kb on chromosome 11q13.3. Human and macaque cDNAs share 96% homology. Human XRRA1 cDNA is 1987 nt long and encodes a protein of 559 aa. XRRA1 protein is highly conserved in human, macaque, mouse, rat, pig, and bovine. GFP-XRRA1 fusion protein was detected in both the nucleus and cytoplasm of HCT116 clones and COS-7 cells. Interestingly, we found evidence that COS-7 cells which over-expressed XRRA1 lacked Ku86 (Ku80, XRCC5), a non-homologous end joining (NHEJ) DNA repair molecule, in the nucleus. RT-PCR analysis showed differential expression of XRRA1 after XR in HCT116 clones manifesting significantly different XR responses. Further, we found that XRRA1 was expressed in most tumor cell types. Surprisingly, mouse Xrra1 was detected in mouse embryonic stem cells R1.

Conclusions: Both XRRA1 cDNA and protein are highly conserved among mammals, suggesting that XRRA1 may have similar functions. Our results also suggest that the genetic modulation of XRRA1 may affect the XR responses of HCT116 clones and that XRRA1 may have a role in the response of human tumor and normal cells to XR. XRRA1 might be correlated with cancer development and might also be an early expressed gene.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC194569PMC
http://dx.doi.org/10.1186/1471-2164-4-32DOI Listing

Publication Analysis

Top Keywords

xrra1
21
tumor cell
12
human macaque
12
xrra1 cdna
12
human xrra1
12
hct116 clones
12
human
10
molecular cloning
8
cloning genomic
8
genomic characterization
8

Similar Publications

Reproductive traits are the basic economic traits of goats and important indicators in goat breeding. In this study, Dazu black goats (DBGs; n = 150), an important Chinese local goat breed with excellent reproductive performance, were used to screen for important variation loci and genes of reproductive traits. Through genome-wide association studies (GWAS), 18 SNPs were found to be associated with kidding traits (average litter size, average litter size in the first three parity, and average litter size in the first six parity), and 10 SNPs were associated with udder traits (udder depth, teat diameter, teat length, and supernumerary teat).

View Article and Find Full Text PDF

Genetic architecture of asthma in African American patients.

J Allergy Clin Immunol

April 2023

Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pa; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pa; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. Electronic address:

Background: Asthma is a chronic inflammatory disorder with a strong genetic inheritance. Although more than 100 loci were reported through the genome-wide association study of European populations, the genetic underpinning of asthma in African American individuals remains largely elusive.

Objective: We aimed to identify genetic loci associated with asthma in African American individuals.

View Article and Find Full Text PDF
Article Synopsis
  • - Chronic arsenic exposure from drinking water is linked to a higher risk of cancer and other diseases, and the impact of alternative splicing on this toxicity and carcinogenicity is not well-studied.
  • - The study aimed to profile alternative splicing changes in human skin cells (keratinocytes) due to long-term arsenic exposure, using RNA sequencing to identify these changes over 28 weeks.
  • - Researchers found over 600 differential splicing events at each checkpoint, affecting various parts of genes, and validated selected splicing predictions through additional tests, reinforcing the connection between arsenic exposure and potential cancer-related changes in gene expression.
View Article and Find Full Text PDF

Unfolding of hidden white blood cell count phenotypes for gene discovery using latent class mixed modeling.

Genes Immun

September 2019

Department of Biomedical Informatics Medical Education, School of Medicine, University of Washington, Seattle, WA, 98109, USA.

Resting-state white blood cell (WBC) count is a marker of inflammation and immune system health. There is evidence that WBC count is not fixed over time and there is heterogeneity in WBC trajectory that is associated with morbidity and mortality. Latent class mixed modeling (LCMM) is a method that can identify unobserved heterogeneity in longitudinal data and attempts to classify individuals into groups based on a linear model of repeated measurements.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!