The convergence of head-on DNA unwinding forks induces helicase oligomerization and activity transition - Archive ouverte HAL Access content directly
Journal Articles Proceedings of the National Academy of Sciences of the United States of America Year : 2022

The convergence of head-on DNA unwinding forks induces helicase oligomerization and activity transition

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Abstract

Helicases are multifunctional motor proteins with the primary task of separating nucleic acid duplexes. These enzymes often exist in distinct oligomeric forms and play essential roles during nucleic acid metabolism. Whether there is a correlation between their oligomeric state and cellular function, and how helicases effectively perform functional switching remains enigmatic. Here, we address these questions using a combined single-molecule approach and Bloom syndrome helicase (BLM). By examining the head-on collision of two BLM-mediated DNA unwinding forks, we find that two groups of BLM, upon fork convergence, promptly oligomerize across the fork junctions and tightly bridge two independent single-stranded (ss) DNA molecules that were newly generated by the unwinding BLMs. This protein oligomerization is mediated by the helicase and RNase D C-terminal (HRDC) domain of BLM and can sustain a disruptive force of up to 300 pN. Strikingly, onsite BLM oligomerization gives rise to an immediate transition of their helicase activities, from unwinding dsDNA to translocating along ssDNA at exceedingly fast rates, thus allowing for the efficient displacement of ssDNA-binding proteins, such as RPA and RAD51. These findings uncover an activity transition pathway for helicases and help to explain how BLM plays both pro- and anti-recombination roles in the maintenance of genome stability.

Dates and versions

inserm-03825786 , version 1 (23-10-2022)

Identifiers

Cite

Lulu Bi, Zhenheng Qin, Teng Wang, Yanan Li, Xinshuo Jia, et al.. The convergence of head-on DNA unwinding forks induces helicase oligomerization and activity transition. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (23), pp.e2116462119. ⟨10.1073/pnas.2116462119⟩. ⟨inserm-03825786⟩
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