Coordinated protein and DNA remodeling by human HLTF and comparison of its activity with Bloom Syndrome helicase protein

Achar Yathish Jagadheesh
Coordinated protein and DNA remodeling by human HLTF and comparison of its activity with Bloom Syndrome helicase protein.
[Thesis] (Unpublished)

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Official URL: http://www.pnas.org/content/early/2011/07/26/11019...

Abstract in foreign language

Human HLTF (Helicase Like Transcription Factor) is a member of the Swi2/Snf2 family of ATP-driven molecular motor proteins. Like many members of Swi2/Snf2 family, HLTF does not exhibit a canonical DNA helicase activity but has an ATP hydrolysis-driven double stranded (ds) DNA translocase activity. The biological importance of HLTF is indicated by the finding that it has a role in replication of damaged DNA and preventing genome rearrangement, and in accord, it is considered as tumor suppressor. The discovery of the replication fork remodeling activity of HLTF, particularly its fork reversal activity, provided a mechanistic explanation for its role in template switch dependent error-free DNA damage bypass. However, a stalled replication fork contains several single-stranded (ss) DNA- and dsDNA-bound proteins such as RPA, RFC, PCNA, and replicative polymerase. How these proteins are displaced before the DNA remodeling occurs has been unknown. Here we examine whether proteins bound to replication fork like DNA structures inhibit fork remodeling by two distinct fork reversal enzymes, namely HLTF, a Swi2/Snf2 family protein, and Blooms syndrome helicase (BLM), a RecQ family helicase. We provide evidence that HLTF can specifically remodel replication forks bound by either dsDNA- or ssDNA-binding proteins, which is associated with a novel protein remodeling activity of HLTF. These observations shed light on how masses of proteins surrounding the stalled replication fork can become displaced from the DNA providing thereby access to new damage bypass players.

Item Type: Thesis (PhD)
Creators: Achar Yathish Jagadheesh
Hungarian title label: A HLTF koordinált fehérje és DNS átrendezése és aktivitásának összehasonlítása a Bloom szindróma helikáz fehérjével
Divisions: Doctoral School of Biology
Discipline label: Natural Sciences > Biology
Defence date label: 2011. December 09.
Item ID: 1089
MTMT id: 2774037
doi: https://doi.org/10.14232/phd.1089
Date Deposited: 2011. Sep. 29. 13:52
Last Modified: 2019. Aug. 28. 15:21
Depository no.: B 4986
URI: http://doktori.bibl.u-szeged.hu/id/eprint/1089
Defence/Citable status: Defended.

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