scholarly journals Somatic role of SYCE2: an insulator that dissociates HP1α from H3K9me3 and potentiates DNA repair

2018 ◽  
Vol 1 (3) ◽  
pp. e201800021
Author(s):  
Noriko Hosoya ◽  
Masato Ono ◽  
Kiyoshi Miyagawa
Keyword(s):  
Dna Damage ◽  
Synaptonemal Complex ◽  
Germ Line ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Exogenous Dna ◽  
Repair Activity ◽  
Break Repair

The synaptonemal complex is a proteinaceous structure essential for meiotic recombination, and its components have been assumed to play a role exclusively in the germ line. However, SYCE2, a component constituting the synaptonemal complex, is expressed at varying levels in somatic cells. Considering its potent protein-binding activities, it may be possible that SYCE2 plays a somatic role by affecting nuclear functions. Here, we show that SYCE2 constitutively insulates HP1α from trimethylated histone H3 lysine 9 (H3K9me3) to promote DNA double-strand break repair. Unlike other HP1α-binding proteins, which use the canonical PXVXL motifs for their bindings, SYCE2 interacts with the chromoshadow domain of HP1α through its N-terminal hydrophobic sequence. SYCE2 reduces HP1α-H3K9me3 binding without affecting H3K9me3 levels and potentiates ataxia telangiectasia mutated–mediated double-strand break repair activity even in the absence of exogenous DNA damage. Such a somatic role of SYCE2 is ubiquitously observed even if its expression levels are low. These findings suggest that SYCE2 plays a somatic role in the link between the nuclear microenvironment and the DNA damage response potentials as a scaffold of HP1α localization.

scholarly journals Role of JC Virus Agnoprotein in DNA Repair

2004 ◽  
Vol 78 (16) ◽  
pp. 8593-8600 ◽  
Author(s):  
Armine Darbinyan ◽  
Khwaja M. Siddiqui ◽  
Dorota Slonina ◽  
Nune Darbinian ◽  
Shohreh Amini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Jc Virus ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
N Terminus ◽  
Repair Activity ◽  
Break Repair

ABSTRACT The late region of human neurotropic JC virus encodes a small 71-amino-acid agnoprotein that is also found in the polyomaviruses simian virus 40 and BK virus. Several functions of agnoprotein have been identified, including roles in regulating viral transcription and virion maturation. Earlier studies showed that agnoprotein expressed alone induced p21/WAF-1 expression and caused cells to accumulate in the G2/M stage of the cell cycle. Here we report that agnoprotein expression sensitized cells to the cytotoxic effects of the DNA-damaging agent cisplatin. Agnoprotein reduced the viability of cisplatin-treated cells and increased chromosome fragmentation and micronucleus formation. Whereas cisplatin-treated control cells accumulated in S phase, cells expressing agnoprotein did not, instead becoming aneuploid. Agnoprotein expression correlated with impaired double-strand-break repair activity in cellular extracts and reduced expression of the Ku70 and Ku80 DNA repair proteins. After agnoprotein expression, much of the Ku70 protein was located in the perinuclear space, where agnoprotein was also found. Results from binding studies showed an interaction of agnoprotein with Ku70 which was mediated by the N terminus. The ability of agnoprotein to inhibit double-strand break repair activity when it was added to cellular extracts was also mediated by the N terminus. We conclude that agnoprotein inhibits DNA repair after DNA damage and interferes with DNA damage-induced cell cycle regulation. Since Ku70 is a subunit of the DNA-dependent protein kinase that is responsible both for double-strand break repair and for signaling damage-induced cell cycle arrest, the modulation of Ku70 and/or Ku80 by agnoprotein may represent an important event in the polyomavirus life cycle and in cell transformation.

scholarly journals Role of the double-strand break repair pathway in the maintenance of genomic stability

2014 ◽  
Vol 2 (1) ◽  
pp. e968020 ◽  
Author(s):  
Tangui Le Guen ◽  
Sandrine Ragu ◽  
Josée Guirouilh-Barbat ◽  
Bernard S Lopez
Keyword(s):  
Genomic Stability ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Repair Pathway ◽  
Break Repair

scholarly journals The nucleoporin 153, a novel factor in double-strand break repair and DNA damage response

Oncogene ◽  
2012 ◽  
Vol 31 (45) ◽  
pp. 4803-4809 ◽  
Author(s):  
C Lemaître ◽  
B Fischer ◽  
A Kalousi ◽  
A-S Hoffbeck ◽  
J Guirouilh-Barbat ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Damage Response ◽  
Break Repair

scholarly journals Involvement of POLA2 in Double Strand Break Repair and Genotoxic Stress

2020 ◽  
Vol 21 (12) ◽  
pp. 4245
Author(s):  
Tuyen T. Dang ◽  
Julio C. Morales
Keyword(s):  
Dna Damage ◽  
Genomic Instability ◽  
Dna Polymerase ◽  
Genotoxic Stress ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Dsb Repair ◽  
Dna Polymerase Alpha ◽  
Break Repair

Cellular survival is dependent on the efficient replication and transmission of genomic information. DNA damage can be introduced into the genome by several different methods, one being the act of DNA replication. Replication is a potent source of DNA damage and genomic instability, especially through the formation of DNA double strand breaks (DSBs). DNA polymerase alpha is responsible for replication initiation. One subunit of the DNA polymerase alpha replication machinery is POLA2. Given the connection between replication and genomic instability, we decided to examine the role of POLA2 in DSB repair, as little is known about this topic. We found that loss of POLA2 leads to an increase in spontaneous DSB formation. Loss of POLA2 also slows DSB repair kinetics after treatment with etoposide and inhibits both of the major double strand break repair pathways: non-homologous end-joining and homologous recombination. In addition, loss of POLA2 leads to increased sensitivity to ionizing radiation and PARP1 inhibition. Lastly, POLA2 expression is elevated in glioblastoma multiforme tumors and correlates with poor overall patient survival. These data demonstrate a role for POLA2 in DSB repair and resistance to genotoxic stress.

Sign in / Sign up

Export Citation Format

Share Document