The set domain is essential for metnase functions in replication restart and the 5' end of ss-overhang cleavage

Hyun Suk Kim, Sung Kyung Kim, Robert Hromas, Suk-Hee Lee

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Metnase (also known as SETMAR) is a chimeric SET-transposase protein that plays essential role(s) in non-homologous end joining (NHEJ) repair and replication fork restart. Although the SET domain possesses histone H3 lysine 36 dimethylation (H3K36me2) activity associated with an improved association of early repair components for NHEJ, its role in replication restart is less clear. Here we show that the SET domain is necessary for the recovery from DNA damage at the replication forks following hydroxyurea (HU) treatment. Cells overexpressing the SET deletion mutant caused a delay in fork restart after HU release. Our In vitro study revealed that the SET domain but not the H3K36me2 activity is required for the 5' end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. Together, our results suggest that the Metnase SET domain has a positive role in restart of replication fork and the 5' end of ss-overhang cleavage, providing a new insight into the functional interaction of the SET and the transposase domains.

Original languageEnglish (US)
Article numbere0139418
JournalPLoS One
Volume10
Issue number10
DOIs
StatePublished - Oct 5 2015

Fingerprint

Transposases
hydroxyurea
Hydroxyurea
Joining
DNA
Repair
histones
in vitro studies
DNA damage
Histones
Lysine
DNA Damage
lysine
mutants
Recovery
Proteins
proteins
cells
In Vitro Techniques

ASJC Scopus subject areas

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

Cite this

The set domain is essential for metnase functions in replication restart and the 5' end of ss-overhang cleavage. / Kim, Hyun Suk; Kim, Sung Kyung; Hromas, Robert; Lee, Suk-Hee.

In: PLoS One, Vol. 10, No. 10, e0139418, 05.10.2015.

Research output: Contribution to journalArticle

Kim, Hyun Suk ; Kim, Sung Kyung ; Hromas, Robert ; Lee, Suk-Hee. / The set domain is essential for metnase functions in replication restart and the 5' end of ss-overhang cleavage. In: PLoS One. 2015 ; Vol. 10, No. 10.
@article{b753fd94ebd6496e8f3e7564f04bcee9,
title = "The set domain is essential for metnase functions in replication restart and the 5' end of ss-overhang cleavage",
abstract = "Metnase (also known as SETMAR) is a chimeric SET-transposase protein that plays essential role(s) in non-homologous end joining (NHEJ) repair and replication fork restart. Although the SET domain possesses histone H3 lysine 36 dimethylation (H3K36me2) activity associated with an improved association of early repair components for NHEJ, its role in replication restart is less clear. Here we show that the SET domain is necessary for the recovery from DNA damage at the replication forks following hydroxyurea (HU) treatment. Cells overexpressing the SET deletion mutant caused a delay in fork restart after HU release. Our In vitro study revealed that the SET domain but not the H3K36me2 activity is required for the 5' end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. Together, our results suggest that the Metnase SET domain has a positive role in restart of replication fork and the 5' end of ss-overhang cleavage, providing a new insight into the functional interaction of the SET and the transposase domains.",
author = "Kim, {Hyun Suk} and Kim, {Sung Kyung} and Robert Hromas and Suk-Hee Lee",
year = "2015",
month = "10",
day = "5",
doi = "10.1371/journal.pone.0139418",
language = "English (US)",
volume = "10",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - The set domain is essential for metnase functions in replication restart and the 5' end of ss-overhang cleavage

AU - Kim, Hyun Suk

AU - Kim, Sung Kyung

AU - Hromas, Robert

AU - Lee, Suk-Hee

PY - 2015/10/5

Y1 - 2015/10/5

N2 - Metnase (also known as SETMAR) is a chimeric SET-transposase protein that plays essential role(s) in non-homologous end joining (NHEJ) repair and replication fork restart. Although the SET domain possesses histone H3 lysine 36 dimethylation (H3K36me2) activity associated with an improved association of early repair components for NHEJ, its role in replication restart is less clear. Here we show that the SET domain is necessary for the recovery from DNA damage at the replication forks following hydroxyurea (HU) treatment. Cells overexpressing the SET deletion mutant caused a delay in fork restart after HU release. Our In vitro study revealed that the SET domain but not the H3K36me2 activity is required for the 5' end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. Together, our results suggest that the Metnase SET domain has a positive role in restart of replication fork and the 5' end of ss-overhang cleavage, providing a new insight into the functional interaction of the SET and the transposase domains.

AB - Metnase (also known as SETMAR) is a chimeric SET-transposase protein that plays essential role(s) in non-homologous end joining (NHEJ) repair and replication fork restart. Although the SET domain possesses histone H3 lysine 36 dimethylation (H3K36me2) activity associated with an improved association of early repair components for NHEJ, its role in replication restart is less clear. Here we show that the SET domain is necessary for the recovery from DNA damage at the replication forks following hydroxyurea (HU) treatment. Cells overexpressing the SET deletion mutant caused a delay in fork restart after HU release. Our In vitro study revealed that the SET domain but not the H3K36me2 activity is required for the 5' end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. Together, our results suggest that the Metnase SET domain has a positive role in restart of replication fork and the 5' end of ss-overhang cleavage, providing a new insight into the functional interaction of the SET and the transposase domains.

UR - http://www.scopus.com/inward/record.url?scp=84947206419&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947206419&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0139418

DO - 10.1371/journal.pone.0139418

M3 - Article

C2 - 26437079

AN - SCOPUS:84947206419

VL - 10

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0139418

ER -