Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice.

Animals Cell Proliferation Cell Transformation, Neoplastic / genetics Colitis / chemically induced DNA Damage Dextran Sulfate Disease Models, Animal Epithelial Cells / enzymology Female Genetic Predisposition to Disease Genomic Instability Humans Intestinal Neoplasms / enzymology Intestine, Small / enzymology Male Mice, Knockout Phenotype Ribonuclease H / deficiency Tumor Suppressor Protein p53 / deficiency

Colon Cancer DNA Repair Mouse Model Ribonucleotide Excision Repair

Journal

Gastroenterology

ISSN: 1528-0012

Titre abrégé: Gastroenterology

Pays: United States

ID NLM: 0374630

Informations de publication

Date de publication:
01 2019

Historique:

received: 27 02 2018

revised: 06 09 2018

accepted: 24 09 2018

pubmed: 3 10 2018

medline: 29 1 2019

entrez: 2 10 2018

Statut: ppublish

Résumé

RNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease H2 subunits A, B, and C), that cleaves RNA:DNA hybrids and removes mis-incorporated ribonucleotides from genomic DNA through ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and produces the most frequent type of naturally occurring DNA lesion. We investigated whether intestinal epithelial proliferation requires RNase H2 function and whether RNase H2 activity is disrupted during intestinal carcinogenesis. We generated mice with epithelial-specific deletion of ribonuclease H2 subunit B (H2b The H2b In analyses of mice with disruption of the ribonuclease H2 subunit B gene and colorectal tumors from patients, we provide evidence that RNase H2 functions as a colorectal tumor suppressor. H2b/p53

Sections du résumé

BACKGROUND & AIMS

METHODS

We generated mice with epithelial-specific deletion of ribonuclease H2 subunit B (H2b

RESULTS

The H2b

CONCLUSIONS

In analyses of mice with disruption of the ribonuclease H2 subunit B gene and colorectal tumors from patients, we provide evidence that RNase H2 functions as a colorectal tumor suppressor. H2b/p53

Identifiants

DOI: 10.1053/j.gastro.2018.09.047 PMID: 30273559 PMC: PMC6311085

pubmed: 30273559

pii: S0016-5085(18)35077-7

doi: 10.1053/j.gastro.2018.09.047

pmc: PMC6311085

pii:

doi:

Substances chimiques

Trp53 protein, mouse 0

Tumor Suppressor Protein p53 0

Dextran Sulfate 9042-14-2

ribonuclease HII EC 3.1.26.-

Ribonuclease H EC 3.1.26.4

ribonuclease H2, mouse EC 3.1.26.4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

145-159.e19

Subventions

Organisme : Medical Research Council

ID : MC_PC_U127580972

Pays : United Kingdom

Organisme : Medical Research Council

ID : U127580972

Pays : United Kingdom

Informations de copyright

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