HELB Is a Feedback Inhibitor of DNA End Resection.

Tkáč, Ján; Xu, Guotai; Adhikary, Hemanta; Young, Jordan T F; Gallo, David; Escribano-Díaz, Cristina; Krietsch, Jana; Orthwein, Alexandre; Munro, Meagan; Sol, Wendy; Al-Hakim, Abdallah; Lin, Zhen-Yuan; Jonkers, Jos; Borst, Piet; Brown, Grant W; Gingras, Anne-Claude; Rottenberg, Sven; Masson, Jean-Yves; Durocher, Daniel (2016). HELB Is a Feedback Inhibitor of DNA End Resection. Molecular cell, 61(3), pp. 405-418. Cell Press 10.1016/j.molcel.2015.12.013

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DNA double-strand break repair by homologous recombination is initiated by the formation of 3' single-stranded DNA (ssDNA) overhangs by a process termed end resection. Although much focus has been given to the decision to initiate resection, little is known of the mechanisms that regulate the ongoing formation of ssDNA tails. Here we report that DNA helicase B (HELB) underpins a feedback inhibition mechanism that curtails resection. HELB is recruited to ssDNA by interacting with RPA and uses its 5'-3' ssDNA translocase activity to inhibit EXO1 and BLM-DNA2, the nucleases catalyzing resection. HELB acts independently of 53BP1 and is exported from the nucleus as cells approach S phase, concomitant with the upregulation of resection. Consistent with its role as a resection antagonist, loss of HELB results in PARP inhibitor resistance in BRCA1-deficient tumor cells. We conclude that mammalian DNA end resection triggers its own inhibition via the recruitment of HELB.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Rottenberg, Sven

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1097-2765

Publisher:

Cell Press

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

07 Jul 2017 14:25

Last Modified:

07 Jul 2017 14:25

Publisher DOI:

10.1016/j.molcel.2015.12.013

PubMed ID:

26774285

BORIS DOI:

10.7892/boris.96723

URI:

https://boris.unibe.ch/id/eprint/96723

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