BLM protein mitigates formaldehyde-induced genomic instability

Anuradha Kumari, Nichole Owen, Eleonora Juarez, Amanda McCullough

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Formaldehyde is a reactive aldehyde that has been classified as a class I human carcinogen by the International Agency for Cancer Research. There are growing concerns over the possible adverse health effects related to the occupational and environmental human exposures to formaldehyde. Although formaldehyde-induced DNA and protein adducts have been identified, the genomic instability mechanisms and the cellular tolerance pathways associated with formaldehyde exposure are not fully characterized. This study specifically examines the role of a genome stability protein, Bloom (BLM) in limiting formaldehyde-induced cellular and genetic abnormalities. Here, we show that in the absence of BLM protein, formaldehyde-treated cells exhibited increased cellular sensitivity, an immediate cell cycle arrest, and an accumulation of chromosome radial structures. In addition, live-cell imaging experiments demonstrated that formaldehyde-treated cells are dependent on BLM for timely segregation of daughter cells. Both wild-type and BLM-deficient formaldehyde-treated cells showed an accumulation of 53BP1 and γH2AX foci indicative of DNA double-strand breaks (DSBs); however, relative to wild-type cells, the BLM-deficient cells exhibited delayed repair of formaldehyde-induced DSBs. In response to formaldehyde exposure, we observed co-localization of 53BP1 and BLM foci at the DSB repair site, where ATM-dependent accumulation of formaldehyde-induced BLM foci occurred after the recruitment of 53BP1. Together, these findings highlight the significance of functional interactions among ATM, 53BP1, and BLM proteins as responders associated with the repair and tolerance mechanisms induced by formaldehyde.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalDNA Repair
Volume28
DOIs
StatePublished - Apr 1 2015

Fingerprint

Genomic Instability
Formaldehyde
Proteins
Cells
Repair
Automatic teller machines
Chromosome Structures
International Agencies
Double-Stranded DNA Breaks
DNA Adducts
Cell Separation
Environmental Exposure
Cell Cycle Checkpoints
Aldehydes
Carcinogens
DNA
Chromosomes
Genes
Health

Keywords

  • 53BP1
  • ATM
  • BLM
  • Double-strand breaks
  • Formaldehyde

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

BLM protein mitigates formaldehyde-induced genomic instability. / Kumari, Anuradha; Owen, Nichole; Juarez, Eleonora; McCullough, Amanda.

In: DNA Repair, Vol. 28, 01.04.2015, p. 73-82.

Research output: Contribution to journalArticle

Kumari, Anuradha ; Owen, Nichole ; Juarez, Eleonora ; McCullough, Amanda. / BLM protein mitigates formaldehyde-induced genomic instability. In: DNA Repair. 2015 ; Vol. 28. pp. 73-82.
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