The Involvement of Human RECQL4 in DNA Double-strand Break Repair

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2010 Mar 13

PMID 20222902

Citations 53

Authors

Dharmendra Kumar Singh

Parimal Karmakar

Maria Aamann

Shepherd H Schurman

Alfred May

Deborah L Croteau

Lynnette Burks

Sharon E Plon

Vilhelm A Bohr

Affiliations

Soon will be listed here.

Abstract

Rothmund-Thomson syndrome (RTS) is an autosomal recessive hereditary disorder associated with mutation in RECQL4 gene, a member of the human RecQ helicases. The disease is characterized by genomic instability, skeletal abnormalities and predisposition to malignant tumors, especially osteosarcomas. The precise role of RECQL4 in cellular pathways is largely unknown; however, recent evidence suggests its involvement in multiple DNA metabolic pathways. This study investigates the roles of RECQL4 in DNA double-strand break (DSB) repair. The results show that RECQL4-deficient fibroblasts are moderately sensitive to gamma-irradiation and accumulate more gammaH2AX and 53BP1 foci than control fibroblasts. This is suggestive of defects in efficient repair of DSB's in the RECQL4-deficient fibroblasts. Real time imaging of live cells using laser confocal microscopy shows that RECQL4 is recruited early to laser-induced DSBs and remains for a shorter duration than WRN and BLM, indicating its distinct role in repair of DSBs. Endogenous RECQL4 also colocalizes with gammaH2AX at the site of DSBs. The RECQL4 domain responsible for its DNA damage localization has been mapped to the unique N-terminus domain between amino acids 363-492, which shares no homology to recruitment domains of WRN and BLM to the DSBs. Further, the recruitment of RECQL4 to laser-induced DNA damage is independent of functional WRN, BLM or ATM proteins. These results suggest distinct cellular dynamics for RECQL4 protein at the site of laser-induced DSB and that it might play important roles in efficient repair of DSB's.

Citing Articles

RECQL4 requires PARP1 for recruitment to DNA damage, and PARG dePARylation facilitates its associated role in end joining.

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Interaction of RECQL4 with poly(ADP-ribose) is critical for the DNA double-strand break response in human cells.

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RECQL4 Inhibits Radiation-Induced Tumor Immune Awakening via Suppressing the cGAS-STING Pathway in Hepatocellular Carcinoma.

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Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase.

Papageorgiou A, Pospisilova M, Cibulka J, Ashraf R, Waudby C, Kaderavek P Nat Commun. 2023; 14(1):6751.

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DNA-PKcs-dependent phosphorylation of RECQL4 promotes NHEJ by stabilizing the NHEJ machinery at DNA double-strand breaks.

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PMID: 35580045 PMC: 9178012. DOI: 10.1093/nar/gkac375.

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