E-resources
-
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
Molecular cell, 02/2016, Volume: 61, Issue: 3Journal Article
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. Display omitted •HELB is recruited to resected DSB ends via an interaction with RPA•HELB uses its 5′-3′ translocase activity to inhibit DNA end resection•Nuclear export of HELB participates in the activation of resection in S phase•HELB loss leads to PARPi resistance in BRCA1-deficient tumor cells Tkáč et al. report that HELB underpins a feedback inhibition mechanism that curtails mammalian DNA end resection. HELB is recruited to ssDNA in an RPA-dependent manner, where it limits long-range resection by the BLM-DNA2 and EXO1 nuclease machineries. Consequently, HELB is critical for the PARP inhibitor sensitivity of BRCA1-deficient tumors.
Author
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.