Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy

Khattar, Ekta; Maung, Kyaw Ze Ya; Chew, Chen Li; Ghosh, Arkasubhra; Mok, Michelle Meng Huang; Lee, Pei; Zhang, Jun; Chor, Wei Hong Jeff; Cildir, Gökhan; Wang, Chelsia Qiuxia; Mohd-Ismail, Nur Khairiah; Chin, Desmond Wai Loon; Lee, Soo Chin; Yang, Henry; Shin, Yong Jae; Nam, Do Hyun; Chen, Liming; Kumar, Alan Prem; Deng, Lih Wen; Ikawa, Masahito; Gunaratne, Jayantha; Osato, Motomi; Tergaonkar, Vinay

doi:https://doi.org/10.1038/s41467-019-13082-9

Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy

Khattar, Ekta; Maung, Kyaw Ze Ya; Chew, Chen Li et al.

Nature Communications, 2019, 10(1), 5349

Number of Access:1,862（2025-08-22 01:08 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/78555

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Title	Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy
Creator	CreatorName Khattar, Ekta
	CreatorName Maung, Kyaw Ze Ya
	CreatorName Chew, Chen Li
	CreatorName Ghosh, Arkasubhra
	CreatorName Mok, Michelle Meng Huang
	CreatorName Lee, Pei
	CreatorName Zhang, Jun
	CreatorName Chor, Wei Hong Jeff
	CreatorName Cildir, Gökhan
	CreatorName Wang, Chelsia Qiuxia
	CreatorName Mohd-Ismail, Nur Khairiah
	CreatorName Chin, Desmond Wai Loon
	CreatorName Lee, Soo Chin
	CreatorName Yang, Henry
	CreatorName Shin, Yong Jae
	CreatorName Nam, Do Hyun
	CreatorName Chen, Liming
	CreatorName Kumar, Alan Prem
	CreatorName Deng, Lih Wen
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	CreatorName Gunaratne, Jayantha
	CreatorName Osato, Motomi
	CreatorName Tergaonkar, Vinay
Description	Khattar, E., Maung, K.Z.Y., Chew, C.L. et al. Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy. Nat Commun 10, 5349 (2019). https://doi.org/10.1038/s41467-019-13082-9
Abstract	Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the telomere or with its known partner TRF2. We show that RAP1 interacts with many members of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	10(1)
Page	5349
Date of Issued	2019-12-13
Language	English
Handle URL	https://hdl.handle.net/11094/78555
eISSN	20411723
NCID	AA12645905
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-019-13082-9
Relation.isIdenticalTo	PMID 31836706
Access Rights	open access
CopyRight	© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Nature Communications. 2019, 10(1), p. 5349
DC.title	Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy
DC.creator	Khattar, Ekta
	Maung, Kyaw Ze Ya
	Chew, Chen Li
	Ghosh, Arkasubhra
	Mok, Michelle Meng Huang
	Lee, Pei
	Zhang, Jun
	Chor, Wei Hong Jeff
	Cildir, Gökhan
	Wang, Chelsia Qiuxia
	Mohd-Ismail, Nur Khairiah
	Chin, Desmond Wai Loon
	Lee, Soo Chin
	Yang, Henry
	Shin, Yong Jae
	Nam, Do Hyun
	Chen, Liming
	Kumar, Alan Prem
	Deng, Lih Wen
	Ikawa, Masahito
	Gunaratne, Jayantha
	Osato, Motomi
	Tergaonkar, Vinay
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-12-13
DC.identifier	https://doi.org/10.1038/s41467-019-13082-9
DC.description	Khattar, E., Maung, K.Z.Y., Chew, C.L. et al. Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy. Nat Commun 10, 5349 (2019). https://doi.org/10.1038/s41467-019-13082-9
DCTERMS.abstract	Increased levels and non-telomeric roles have been reported for shelterin proteins, including RAP1 in cancers. Herein using Rap1 null mice, we provide the genetic evidence that mammalian Rap1 plays a major role in hematopoietic stem cell survival, oncogenesis and response to chemotherapy. Strikingly, this function of RAP1 is independent of its association with the telomere or with its known partner TRF2. We show that RAP1 interacts with many members of the DNA damage response (DDR) pathway. RAP1 depleted cells show reduced interaction between XRCC4/DNA Ligase IV and DNA-PK, and are impaired in DNA Ligase IV recruitment to damaged chromatin for efficient repair. Consistent with its role in DNA damage repair, RAP1 loss decreases double-strand break repair via NHEJ in vivo, and consequently reduces B cell class switch recombination. Finally, we discover that RAP1 levels are predictive of the success of chemotherapy in breast and colon cancer.
DC.rights	© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	78555
citation_title	Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy
citation_author	Khattar, Ekta
	Maung, Kyaw Ze Ya
	Chew, Chen Li
	Ghosh, Arkasubhra
	Mok, Michelle Meng Huang
	Lee, Pei
	Zhang, Jun
	Chor, Wei Hong Jeff
	Cildir, Gökhan
	Wang, Chelsia Qiuxia
	Mohd-Ismail, Nur Khairiah
	Chin, Desmond Wai Loon
	Lee, Soo Chin
	Yang, Henry
	Shin, Yong Jae
	Nam, Do Hyun
	Chen, Liming
	Kumar, Alan Prem
	Deng, Lih Wen
	Ikawa, Masahito
	Gunaratne, Jayantha
	Osato, Motomi
	Tergaonkar, Vinay
citation_publisher	Nature Research
citation_language	English
citation_date	2019-12-13
citation_journal_title	Nature Communications
citation_volume	10
citation_issue	1
citation_firstpage	5349
citation_doi	https://doi.org/10.1038/s41467-019-13082-9
citation_pmid	31836706
citation_public_url	https://hdl.handle.net/11094/78555

Rap1 regulates hematopoietic stem cell survival and affects oncogenesis and response to chemotherapy

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