The 53BP1 Homolog in C. elegans Influences DNA Repair and Promotes Apoptosis in Response to Ionizing Radiation

Jin Sun Ryu, Sang Jo Kang, Hyeon Sook Koo

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ) in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs), as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog) was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.

Original languageEnglish
Article numbere64028
JournalPloS one
Volume8
Issue number5
DOIs
Publication statusPublished - 2013 May 10

Fingerprint

Double-Stranded DNA Breaks
Ionizing radiation
DNA repair
Ionizing Radiation
ionizing radiation
DNA Repair
Repair
apoptosis
Apoptosis
DNA
Cells
Cell Cycle Checkpoints
mutation
Mutation
Joining
chromosome aberrations
Germ Cells
Chromosome Aberrations
hypersensitivity
DNA damage

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

@article{880ce3a3337d4e169b2342fd4d10f8d1,
title = "The 53BP1 Homolog in C. elegans Influences DNA Repair and Promotes Apoptosis in Response to Ionizing Radiation",
abstract = "53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ) in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs), as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog) was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.",
author = "Ryu, {Jin Sun} and Kang, {Sang Jo} and Koo, {Hyeon Sook}",
year = "2013",
month = "5",
day = "10",
doi = "10.1371/journal.pone.0064028",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

The 53BP1 Homolog in C. elegans Influences DNA Repair and Promotes Apoptosis in Response to Ionizing Radiation. / Ryu, Jin Sun; Kang, Sang Jo; Koo, Hyeon Sook.

In: PloS one, Vol. 8, No. 5, e64028, 10.05.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The 53BP1 Homolog in C. elegans Influences DNA Repair and Promotes Apoptosis in Response to Ionizing Radiation

AU - Ryu, Jin Sun

AU - Kang, Sang Jo

AU - Koo, Hyeon Sook

PY - 2013/5/10

Y1 - 2013/5/10

N2 - 53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ) in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs), as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog) was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.

AB - 53BP1 contributes to activation of the G2/M checkpoint downstream of ATM and MDC1 in response to ionizing radiation and promotes nonhomologous end-joining (NHEJ) in mammalian cells. In order to determine whether the cellular activities of 53BP1 are conserved in the model organism C. elegans, we analyzed the function of its homolog, HSR-9 in response to DNA damage. Deletion or Mos1-insertion in hsr-9 did not affect the sensitivity of worms to double strand DNA breaks (DSBs), as reflected in embryonic survival and larval development. Nevertheless, the hsr-9 mutations, as well as a lig-4 deletion, reversed the hypersensitivity of rad-54-deficient worms to DSBs. In addition, oocyte chromosomal aberrations, which were increased by rad-54 knockdown in response to DSBs, were also reduced by the hsr-9 mutations. The hsr-9 mutations did not prevent the cell cycle arrest induced by DSBs in mitotically proliferating germ cells. However, they attenuated apoptosis induced by DSBs, but not when CEP-1 (a p53 ortholog) was absent, suggesting that HSR-9 functions in the same pathway as CEP-1. We concluded that the 53BP1 homolog in C. elegans is not directly involved in cell cycle arrest in response to DSBs, but that it promotes apoptosis and also a form of NHEJ that occurs only when rad-54 is deficient.

UR - http://www.scopus.com/inward/record.url?scp=84877265410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877265410&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0064028

DO - 10.1371/journal.pone.0064028

M3 - Article

C2 - 23667696

AN - SCOPUS:84877265410

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 5

M1 - e64028

ER -