RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks

Huiming Lu, Raghavendra A. Shamanna, Guido Keijzers, Roopesh Anand, Lene Juel Rasmussen, Petr Cejka, Deborah L. Croteau, Vilhelm A. Bohr

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 5' end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4’s helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4’s unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.

Original languageEnglish (US)
Pages (from-to)161-173
Number of pages13
JournalCell Reports
Volume16
Issue number1
DOIs
StatePublished - Jun 28 2016
Externally publishedYes

Fingerprint

Double-Stranded DNA Breaks
Homologous Recombination
Repair
DNA
Rothmund-Thomson Syndrome
RecQ Helicases
Recombinational DNA Repair
Exonucleases
Genomic Instability
Lasers
Genes
Aging of materials
1,2-di-(4-sulfamidophenyl)-4-butylpyrazolidine-3,5-dione
Neoplasms
Processing

Keywords

  • DNA repair
  • DNA resection
  • homologous recombination
  • RecQ-like helicase
  • RECQL4
  • Rothmund-Thomson syndrome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lu, H., Shamanna, R. A., Keijzers, G., Anand, R., Rasmussen, L. J., Cejka, P., ... Bohr, V. A. (2016). RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks. Cell Reports, 16(1), 161-173. https://doi.org/10.1016/j.celrep.2016.05.079

RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks. / Lu, Huiming; Shamanna, Raghavendra A.; Keijzers, Guido; Anand, Roopesh; Rasmussen, Lene Juel; Cejka, Petr; Croteau, Deborah L.; Bohr, Vilhelm A.

In: Cell Reports, Vol. 16, No. 1, 28.06.2016, p. 161-173.

Research output: Contribution to journalArticle

Lu, H, Shamanna, RA, Keijzers, G, Anand, R, Rasmussen, LJ, Cejka, P, Croteau, DL & Bohr, VA 2016, 'RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks', Cell Reports, vol. 16, no. 1, pp. 161-173. https://doi.org/10.1016/j.celrep.2016.05.079
Lu H, Shamanna RA, Keijzers G, Anand R, Rasmussen LJ, Cejka P et al. RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks. Cell Reports. 2016 Jun 28;16(1):161-173. https://doi.org/10.1016/j.celrep.2016.05.079
Lu, Huiming ; Shamanna, Raghavendra A. ; Keijzers, Guido ; Anand, Roopesh ; Rasmussen, Lene Juel ; Cejka, Petr ; Croteau, Deborah L. ; Bohr, Vilhelm A. / RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks. In: Cell Reports. 2016 ; Vol. 16, No. 1. pp. 161-173.
@article{272a6c3530e345fabe43e51aa4dbbafb,
title = "RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks",
abstract = "The RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 5' end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4’s helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4’s unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.",
keywords = "DNA repair, DNA resection, homologous recombination, RecQ-like helicase, RECQL4, Rothmund-Thomson syndrome",
author = "Huiming Lu and Shamanna, {Raghavendra A.} and Guido Keijzers and Roopesh Anand and Rasmussen, {Lene Juel} and Petr Cejka and Croteau, {Deborah L.} and Bohr, {Vilhelm A.}",
year = "2016",
month = "6",
day = "28",
doi = "10.1016/j.celrep.2016.05.079",
language = "English (US)",
volume = "16",
pages = "161--173",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - RECQL4 Promotes DNA End Resection in Repair of DNA Double-Strand Breaks

AU - Lu, Huiming

AU - Shamanna, Raghavendra A.

AU - Keijzers, Guido

AU - Anand, Roopesh

AU - Rasmussen, Lene Juel

AU - Cejka, Petr

AU - Croteau, Deborah L.

AU - Bohr, Vilhelm A.

PY - 2016/6/28

Y1 - 2016/6/28

N2 - The RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 5' end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4’s helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4’s unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.

AB - The RecQ helicase RECQL4, mutated in Rothmund-Thomson syndrome, regulates genome stability, aging, and cancer. Here, we identify a crucial role for RECQL4 in DNA end resection, which is the initial and an essential step of homologous recombination (HR)-dependent DNA double-strand break repair (DSBR). Depletion of RECQL4 severely reduces HR-mediated repair and 5' end resection in vivo. RECQL4 physically interacts with MRE11-RAD50-NBS1 (MRN), which senses DSBs and initiates DNA end resection with CtIP. The MRE11 exonuclease regulates the retention of RECQL4 at laser-induced DSBs. RECQL4 also directly interacts with CtIP via its N-terminal domain and promotes CtIP recruitment to the MRN complex at DSBs. Moreover, inactivation of RECQL4’s helicase activity impairs DNA end processing and HR-dependent DSBR without affecting its interaction with MRE11 and CtIP, suggesting an important role for RECQL4’s unwinding activity in the process. Thus, we report that RECQL4 is an important participant in HR-dependent DSBR.

KW - DNA repair

KW - DNA resection

KW - homologous recombination

KW - RecQ-like helicase

KW - RECQL4

KW - Rothmund-Thomson syndrome

UR - http://www.scopus.com/inward/record.url?scp=85008237828&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008237828&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.05.079

DO - 10.1016/j.celrep.2016.05.079

M3 - Article

VL - 16

SP - 161

EP - 173

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 1

ER -