A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Abstract Text:

Pamela Kanellis,Mark Gagliardi,Judit P Banath,Rachel K Szilard,Shinichiro Nakada,Sarah Galicia,Frederic D Sweeney,Diane C Cabelof,Peggy L Olive,Daniel Durocher,Pamela Kanellis,Mark Gagliardi,Judit P Banath,Rachel K Szilard,Shinichiro Nakada,Sarah Galicia,Frederic D Sweeney,Diane C Cabelof,Peggy L Olive,Daniel Durocher,

Genome instability is a hallmark of cancer cells. One class of genome aberrations prevalent in tumor cells is termed gross chromosomal rearrangements (GCRs). GCRs comprise chromosome translocations, amplifications, inversions, deletion of whole chromosome arms, and interstitial deletions. Here, we report the results of a genome-wide screen in Saccharomyces cerevisiae aimed at identifying novel suppressors of GCR formation. The most potent novel GCR suppressor identified is BUD16, the gene coding for yeast pyridoxal kinase (Pdxk), a key enzyme in the metabolism of pyridoxal 5' phosphate (PLP), the biologically active form of vitamin B6. We show that Pdxk potently suppresses GCR events by curtailing the appearance of DNA lesions during the cell cycle. We also show that pharmacological inhibition of Pdxk in human cells leads to the production of DSBs and activation of the DNA damage checkpoint. Finally, our evidence suggests that PLP deficiency threatens genome integrity, most likely via its role in dTMP biosynthesis, as Pdxk-deficient cells accumulate uracil in their nuclear DNA and are sensitive to inhibition of ribonucleotide reductase. Since Pdxk links diet to genome stability, our work supports the hypothesis that dietary micronutrients reduce cancer risk by curtailing the accumulation of DNA damage and suggests that micronutrient depletion could be part of a defense mechanism against hyperproliferation.

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Publishing Authors By Initials

P Kanellis,M Gagliardi,JP Banath,RK Szilard,S Nakada,S Galicia,FD Sweeney,DC Cabelof,PL Olive,D Durocher,P Kanellis,M Gagliardi,JP Banath,RK Szilard,S Nakada,S Galicia,FD Sweeney,DC Cabelof,PL Olive,D Durocher,

For similar genetic processes: mutagenesis: suppression, genetic research abstracts see: genetic processes: mutagenesis: suppression, genetic research

PUBMED ID PMID:

MEDLINE DATE:

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: PLoS genetics

VOLUME: 3

Page Numbers: e134

Journal Abbreviation: PLoS Genet.

ISSN: 1553-7404

DAY: 10

MONTH: Aug

YEAR: 2007

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101239074

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Keywords Mesh Terms:

KEYWORDS: Suppression, Genetic

MESH TERMS: physiology

Chemical & Substance for Abstract: A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions. Information

Substance Name: Pyridoxal Kinase

Registry Number: EC 2.7.1.35

Grant and Affiliation Information for A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.

AFFILIATION: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.

Country: United States

AGENCY: United States NIEHS

GRANT: 1F32-ES013643

ACRONYM: ES

MEDLINETA: PLoS Genet

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions Related Publications

• A screen for suppressors of gross chromosomal rearrangements identifies a conserved role for PLP in preventing DNA lesions.
• Analysis of GADD45A sequence variations in French Canadian families with high risk of breast cancer.
• Can dynamic indicators help the prediction of fluid responsiveness in spontaneously breathing critically ill patients?
• Dun1 counts on rad53 to be turned on.
• Engineering a DNA damage response without DNA damage.
• Factors predicting bacterial involvement in severe acute exacerbations of chronic obstructive pulmonary disease.
• Genetic variants and haplotype analyses of the ZBRK1/ZNF350 gene in high-risk non BRCA1/2 French Canadian breast and ovarian cancer families.
• Germline mutations in the breast cancer susceptibility gene PTEN are rare in high-risk non-BRCA1/2 French Canadian breast cancer families.
• Intimate partner violence before and during pregnancy: experiences of postpartum women in Karachi, Pakistan.
• Mutational analysis of the breast cancer susceptibility gene BRIP1 /BACH1/FANCJ in high-risk non-BRCA1/BRCA2 breast cancer families.
• Opposing roles of syndecan-1 and syndecan-2 in polyethyleneimine-mediated gene delivery.
• Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase.
• PP4 is a gammaH2AX phosphatase required for recovery from the DNA damage checkpoint.
• Relationship between immunosuppression and intensive care unit-acquired multidrug-resistant bacteria: a case-control study.
• Risk factors for relapse of ventilator-associated pneumonia related to nonfermenting Gram negative bacilli: a case-control study.
• Stable high volumetric production of glycosylated human recombinant IFNalpha2b in HEK293 cells.
• [Not Available.]