Evidence map›Paper›PMID 29399538›Full record

ArticleJournal of gastroenterology and hepatology research2017

Impact of RAD51C-mediated Homologous Recombination on Genomic Integrity in Barrett's Adenocarcinoma Cells.

Jagannath Pal, Purushothama Nanjappa, Subodh Kumar, Jialan Shi, Leutz Buon, Nikhil C Munshi, Masood A Shammas

Open access · hybridAbstract read
In one paragraph

Article in Journal of gastroenterology and hepatology research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.4field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Single-Strand Annealing in Cancer.International journal of molecular sciences · 2021
    Review
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Jagannath PalDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States. Multi-disciplinary Research Units (MRUs), Pt J.N.M. Medical College, Raipur, CG, India.
Purushothama NanjappaDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States.
Subodh KumarDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States.
Jialan ShiDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States. Department of Medicine, Harvard Medical School, Boston, MA, the United States.
Leutz BuonDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States.
Nikhil C MunshiDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States. Department of Medicine, Harvard Medical School, Boston, MA, the United States.
Masood A ShammasDepartment of Adult Oncology, Harvard (Dana Farber) Cancer Institute, Boston, MA, the United States. VA Health Care System, West Roxbury, MA, the United States.
Dana-Farber Cancer Institute · USHarvard University · USPt. Jawahar Lal Nehru Memorial Medical College · IN

Funding

Targeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Jill Corre · 2011 to 2026
$32.5M
Telomerase And Homologous Recombination As Targets In Barrett's AdenocarcinomaR01CA125711 · NCI · WAYNE STATE UNIVERSITY · PI SHAMMAS, MASOOD A · 2008 to 2012
$1.7M
NCI NIH HHS P01 CA155258NCI NIH HHS R01 CA125711
6 · The paper itself

Abstract

backgroundIn normal cells, RAD51-mediated homologous recombination (HR) is a precise DNA repair mechanism which plays a key role in the maintenance of genomic integrity and stability. However, elevated (dysregulated) RAD51 is implicated in genomic instability and is a potential target for treatment of certain cancers, including Barrett's adenocarcinoma (BAC). In this study, we investigated genomic impact and translational significance of moderate vs. strong suppression of RAD51 in BAC cells.

methodsBAC cells (FLO-1 and OE33) were transduced with non-targeting control (CS) or RAD51-specific shRNAs, mediating a moderate (40-50%) suppression or strong (80-near 100%) suppression of the gene. DNA breaks, spontaneous or following exposure to DNA damaging agent, were examined by comet assay and 53BP1 staining. Gene expression was monitored by microarrays (Affymetrix). Homologous recombination (HR) and single strand annealing (SSA) activities were measured using plasmid based assays.

resultsWe show that although moderate suppression consistenly inhibits/reduces HR activity, the strong suppression is associated with increase in HR activity (by ~15 - ≥ 50% in various experiments), suggesting activation of RAD51-independent pathway. Contrary to moderate suppression, a strong suppression of RAD51 is associated with a significant induced DNA breaks as well as altered expression of genes involved in detection/processing of DNA breaks and apoptosis. Stronger RAD51 suppression was also associated with mutagenic single strand annealing mediated HR. Suppression of RAD51C inhibited RAD51-independent (SSA-mediated) HR in BAC cells.

conclusionElevated (dysregulated) RAD51 in BAC is implicated in both the repair of DNA breaks as well as ongoing genomic rearrangements. Moderate suppression of this gene reduces HR activity, whereas strong or near complete suppression of this gene activates RAD51C-dependent HR involving a mechanism known as single strand annealing (SSA). SSA-mediated HR, which is a mutagenic HR pathway, further disrupts genomic integrity by increasing DNA breaks in BAC cells.

Indexed as

DNA BreaksEsophageal adenocarcinomaGenomic IntegrityHomologous RecombinationRAD51RAD51CSingle Strand Annealing

Identifiers

PMID29399538
PMCPMC5796564
OpenAlexW2598228858

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.