EMAIL THIS PAGE TO A FRIEND

Oncotarget

CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage.


PMID 26158765

Abstract

Cell cycle and apoptosis regulator 2 (CCAR2, formerly known as DBC1) is a nuclear protein largely involved in DNA damage response, apoptosis, metabolism, chromatin structure and transcription regulation. Upon DNA lesions, CCAR2 is phosphorylated by the apical kinases ATM/ATR and this phosphorylation enhances CCAR2 binding to SIRT1, leading to SIRT1 inhibition, p53 acetylation and p53-dependent apoptosis. Recently, we found that also the checkpoint kinase Chk2 and the proteasome activator REGγ are required for efficient CCAR2-mediated inhibition of SIRT1 and induction of p53-dependent apoptosis.Here, we report that CCAR2 is required for the repair of heterochromatic DNA lesions, as cells knock-out for CCAR2 retain, at late time-points after genotoxic treatment, abnormal levels of DNA damage-associated nuclear foci, whose timely resolution is reinstated by HP1β depletion. Conversely, repair of DNA damages in euchromatin are not affected by CCAR2 absence.We also report that the impairment in heterochromatic DNA repair is caused by defective Chk2 activation, detectable in CCAR2 ablated cells, which finally impacts on the phosphorylation of the Chk2 substrate KAP1 that is required for the induction of heterochromatin relaxation and DNA repair.These studies further extend and confirm the role of CCAR2 in the DNA damage response and DNA repair and illustrate a new mechanism of Chk2 activity regulation. Moreover, the involvement of CCAR2 in the repair of heterochromatic DNA breaks suggests a new role for this protein in the maintenance of chromosomal stability, which is necessary to prevent cancer formation.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

B4436
Anti-53BP1 (C-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
B4561
Anti-53BP1 (N-terminal) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
GW21552 Anti-CHEK2 antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB1407116
Anti-CHEK2 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA001878
Anti-CHEK2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV30290
Anti-CHEK2 antibody produced in rabbit, affinity isolated antibody
SAB2100415
Anti-CHEK2 antibody produced in rabbit, affinity isolated antibody
SAB3500192
Anti-Chk2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
C9108 Anti-Chk2 antibody, Mouse monoclonal, clone DCS-273, purified from hybridoma cell culture
C9233
Anti-Chk2 antibody, Mouse monoclonal, clone DCS-270, purified from hybridoma cell culture
HPA008788
Anti-TP53BP1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA022133
Anti-TP53BP1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
PLA0303
Goat anti-53BP1 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
WH0011200M1
Monoclonal Anti-CHEK2 antibody produced in mouse, clone 4B7, purified immunoglobulin, buffered aqueous solution
SAB1404917
Monoclonal Anti-CHEK2 antibody produced in mouse, clone 4F10, purified immunoglobulin, buffered aqueous solution
WH0007158M1
Monoclonal Anti-TP53BP1 antibody produced in mouse, clone 1B9, purified immunoglobulin, buffered aqueous solution
PLA0077
Rabbit anti-53BP1 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
PLA0122
Rabbit anti-Chk2 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.