Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage

Feng Gong, Deirdre Fahy, Hong Liu, Weidong Wang, Michael J. Smerdon

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G1/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/ Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21.

Original languageEnglish
Pages (from-to)1069-1076
Number of pages8
JournalCell Cycle
Volume7
Issue number8
StatePublished - Apr 15 2008

Fingerprint

Chromatin Assembly and Disassembly
Chromatin
Cells
Ultraviolet radiation
DNA
Irradiation
Apoptosis
DNA Damage
Regain
Proliferating Cell Nuclear Antigen
Carrier Proteins
Repair
Genes
Chemical activation
Radiation
Degradation
Defects
Ultraviolet Rays
Cell Cycle Checkpoints
S Phase

Keywords

  • BAF complex
  • Checkpoint
  • Chromatin remodeling
  • DNA repair
  • Gadd45a
  • p21
  • Swi/Snf
  • UV damage response

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Gong, F., Fahy, D., Liu, H., Wang, W., & Smerdon, M. J. (2008). Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage. Cell Cycle, 7(8), 1069-1076.

Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage. / Gong, Feng; Fahy, Deirdre; Liu, Hong; Wang, Weidong; Smerdon, Michael J.

In: Cell Cycle, Vol. 7, No. 8, 15.04.2008, p. 1069-1076.

Research output: Contribution to journalArticle

Gong, F, Fahy, D, Liu, H, Wang, W & Smerdon, MJ 2008, 'Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage', Cell Cycle, vol. 7, no. 8, pp. 1069-1076.
Gong, Feng ; Fahy, Deirdre ; Liu, Hong ; Wang, Weidong ; Smerdon, Michael J. / Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage. In: Cell Cycle. 2008 ; Vol. 7, No. 8. pp. 1069-1076.
@article{ad7039e13206433a993579cfeb222b4b,
title = "Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage",
abstract = "Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G1/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/ Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21.",
keywords = "BAF complex, Checkpoint, Chromatin remodeling, DNA repair, Gadd45a, p21, Swi/Snf, UV damage response",
author = "Feng Gong and Deirdre Fahy and Hong Liu and Weidong Wang and Smerdon, {Michael J.}",
year = "2008",
month = "4",
day = "15",
language = "English",
volume = "7",
pages = "1069--1076",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "8",

}

TY - JOUR

T1 - Role of the mammalian SWI/SNF chromatin remodeling complex in the cellular response to UV damage

AU - Gong, Feng

AU - Fahy, Deirdre

AU - Liu, Hong

AU - Wang, Weidong

AU - Smerdon, Michael J.

PY - 2008/4/15

Y1 - 2008/4/15

N2 - Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G1/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/ Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21.

AB - Mammalian cells exhibit complex cellular responses to DNA damage, including cell cycle arrest, DNA repair and apoptosis. Defects in any one of these responses can result in carcinogenesis. Absence of the chromatin remodeling complex Swi/Snf is found in many instances of cancer, and we have investigated its role in the UV damage response. The human carcinoma cell line SW13 is deficient in Swi/Snf and is very sensitive to UV radiation. In contrast, SW13 cells with ectopic Brg1 expression regain active Swi/Snf and become significantly more resistant to UV radiation. Sensitivity to UV light correlates well with dramatic UV induced apoptosis in SW13 cells, but not in SW13 cells expressing Brg1. We show that SW13 cells synchronized at the G1/S border progress into S phase after UV irradiation, and this checkpoint deficiency is corrected after Brg1 expression is restored. Interestingly, Brg1 expression in SW13 cells restores expression of two DNA damage responsive genes, Gadd45a and p21. Furthermore, Gadd45a induction and p21 degradation were observed in the Brg1-expressing SW13 cells after UV irradiation. Our findings demonstrate that Swi/ Snf protects cells against deleterious consequences of UV induced DNA damage. These results also indicate that Swi/Snf may modulate checkpoint activation after UV damage via regulation of the two PCNA-binding proteins Gadd45a and p21.

KW - BAF complex

KW - Checkpoint

KW - Chromatin remodeling

KW - DNA repair

KW - Gadd45a

KW - p21

KW - Swi/Snf

KW - UV damage response

UR - http://www.scopus.com/inward/record.url?scp=43549092406&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43549092406&partnerID=8YFLogxK

M3 - Article

C2 - 18414052

AN - SCOPUS:43549092406

VL - 7

SP - 1069

EP - 1076

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 8

ER -