Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

Maciej Kliszczak; Hana Sedlackova; Ganesha P Pitchai; Werner W Streicher; Lumir Krejci; Ian D Hickson

doi:10.18632/oncotarget.6342

Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

Maciej Kliszczak, Hana Sedlackova, Ganesha P Pitchai, Werner W Streicher, Lumir Krejci, Ian D Hickson

15 Citations (Scopus)

Abstract

DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.

Original language	English
Journal	OncoTarget
Volume	6
Issue number	38
Pages (from-to)	40464-79
Number of pages	16
ISSN	1949-2553
DOIs	https://doi.org/10.18632/oncotarget.6342
Publication status	Published - 1 Dec 2015

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title = "Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells",

abstract = "DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.",

author = "Maciej Kliszczak and Hana Sedlackova and Pitchai, {Ganesha P} and Streicher, {Werner W} and Lumir Krejci and Hickson, {Ian D}",

year = "2015",

month = dec,

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doi = "10.18632/oncotarget.6342",

language = "English",

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T1 - Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

AU - Kliszczak, Maciej

AU - Sedlackova, Hana

AU - Pitchai, Ganesha P

AU - Streicher, Werner W

AU - Krejci, Lumir

AU - Hickson, Ian D

PY - 2015/12/1

Y1 - 2015/12/1

N2 - DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.

AB - DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.

U2 - 10.18632/oncotarget.6342

DO - 10.18632/oncotarget.6342

M3 - Journal article

C2 - 26588054

SN - 1949-2553

VL - 6

SP - 40464

EP - 40479

JO - Oncotarget

JF - Oncotarget

IS - 38

ER -

Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

Abstract

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