Involvement of a chromatin remodeling complex in damage tolerance during DNA replication.
ATP-dependent chromatin remodeling complexes have been shown to participate in DNA replication in addition to transcription and DNA repair. However, the mechanisms of their involvement in DNA replication remain unclear. Here, we reveal a specific function of the yeast INO80 chromatin remodeling complex in the DNA damage tolerance pathways. Whereas INO80 is necessary for the resumption of replication at forks stalled by methyl methane sulfonate (MMS), it is not required for replication fork collapse after treatment with hydroxyurea (HU). Mechanistically, INO80 regulates DNA damage tolerance during replication through modulation of PCNA (proliferating cell nuclear antigen) ubiquitination and Rad51-mediated processing of recombination intermediates at impeded replication forks. Our findings establish a mechanistic link between INO80 and DNA damage tolerance pathways, indicating that chromatin remodeling is important for accurate DNA replication.
Department of Carcinogenesis, Science Park Research Division, MD Anderson Cancer Center, Smithville, Texas, USA.
Karina B
KB
Falbo
Constance
C
Alabert
Yuki
Y
Katou
Su
S
Wu
Junhong
J
Han
Tammy
T
Wehr
Jing
J
Xiao
Xiangwei
X
He
Zhiguo
Z
Zhang
Yang
Y
Shi
Katsu
K
Shirahige
Philippe
P
Pasero
Xuetong
X
Shen
D042002:Chromatin Assembly and Disassembly / Q000235:genetics / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005434:Flow Cytometry; D006918:Hydroxyurea / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D018809:Proliferating Cell Nuclear Antigen; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D006918:Hydroxyurea