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Oncofetal HMGA2 effectively curbs unconstrained (+) and (-) DNA supercoiling
Xiaodan Zhao1, Sabrina Peter2, Peter Dröge3
1Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore, 117411, Singapore.
Scientific Reports
|August 18, 2017
Summary
High mobility group A2 (HMGA2) protein stabilizes DNA replication forks. This study shows HMGA2 binds supercoiled DNA, preventing collapse during replication stress and chemotherapy.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- High mobility group A2 (HMGA2) is an HMG protein that binds AT-rich DNA.
- HMGA2 acts as a replication fork chaperone, protecting cells from chemotherapeutic agents.
- Its binding at replication forks is a recently discovered function.
Purpose of the Study:
- To investigate HMGA2 binding to various DNA structures found at replication forks.
- To elucidate the mechanism by which HMGA2 stabilizes replication forks.
Main Methods:
- Studied HMGA2 binding to double-stranded DNA, single-stranded DNA, forked DNA, and supercoiled DNA plectonemes.
- Assessed the effect of HMGA2 binding on supercoiled DNA stability using type I topoisomerase.
Main Results:
- HMGA2 exhibited binding to supercoiled DNA at the lowest concentration.
- HMGA2 binding transiently stabilized supercoiled plectonemes against relaxation by topoisomerase I.
- This suggests a role in preventing replication fork collapse.
Conclusions:
- HMGA2 binding to supercoiled DNA may stabilize parental duplexes during replication stress.
- This stabilization offers a mechanism for attenuating replication fork regression and collapse.
- HMGA2's role as a replication fork chaperone is further supported.
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