Challenges to DNA replication in hypoxic conditions

The term hypoxia refers to any condition where insufficient oxygen is available and therefore encompasses a range of actual oxygen concentrations. The regions of tumours adjacent to necrotic areas are at almost anoxic levels and are known to be extremely therapy resistant (radiobiological hypoxia)....

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Bibliographic Details
Published in:The FEBS journal Vol. 285; no. 9; pp. 1563 - 1571
Main Authors: Ng, Natalie, Purshouse, Karin, Foskolou, Iosifina P., Olcina, Monica M., Hammond, Ester M.
Format: Journal Article
Language:English
Published: England Blackwell Publishing Ltd 01.05.2018
Subjects:
anaerobic conditions
Animals
Cell Cycle Proteins - physiology
Cell Hypoxia - physiology
Damage accumulation
Damage detection
Deoxyribonucleic acid
Deoxyribonucleotides - metabolism
DNA
DNA biosynthesis
DNA Damage
DNA damage response
DNA Repair
DNA replication
DNA Replication - drug effects
DNA-Binding Proteins - physiology
Humans
Hypoxia
neoplasms
Neoplasms - genetics
Oxygen
Oxygen - pharmacology
reoxygenation
Replication
replication restart
replication stress
ribonucleotide reductase
Ribonucleotide Reductases - metabolism
Stress, Physiological - genetics
therapeutics
Tumor Microenvironment
Tumors
hypoxia
ribonucleotide reductase
replication stress
reoxygenation
DNA damage response
replication restart
ISSN:1742-464X, 1742-4658, 1742-4658
Online Access:Get full text
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Summary:The term hypoxia refers to any condition where insufficient oxygen is available and therefore encompasses a range of actual oxygen concentrations. The regions of tumours adjacent to necrotic areas are at almost anoxic levels and are known to be extremely therapy resistant (radiobiological hypoxia). The biological response to radiobiological hypoxia includes the rapid accumulation of replication stress and subsequent DNA damage response, including both ATR‐ and ATM‐mediated signalling, despite the absence of detectable DNA damage. The causes and consequences of hypoxia‐induced replication stress will be discussed. Ribonucleotide reductase (RNR) is a key enzyme required for the synthesis of nucleotides for subsequent incorporation into DNA. In hypoxic (low oxygen) conditions, the composition of RNR is altered to include a stress specific subunit, RRM2B. RRM2B is adapted to function in hypoxic conditions and therefore continue the synthesis of nucleotides.
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ISSN:1742-464X
1742-4658
1742-4658
DOI:10.1111/febs.14377