The authors proposed that in addition to ataxia‐telangiectasia and Rad3 related (ATR), a MYBL2‐MRN‐ATM replication stress response pathway functioned in ESCs to control DNA replication initiation and prevent genome instability.
[EMBO Reports]
6606345
{6606345:PBBZHNPB}
1
apa
50
default
1
160724
https://www.stemcellsciencenews.com/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22PBBZHNPB%22%2C%22library%22%3A%7B%22id%22%3A6606345%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Blakemore%20et%20al.%22%2C%22parsedDate%22%3A%222021-03-28%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BBlakemore%2C%20D.%2C%20Vilaplana-Lopera%2C%20N.%2C%20Almaghrabi%2C%20R.%2C%20Gonzalez%2C%20E.%2C%20Moya%2C%20M.%2C%20Ward%2C%20C.%2C%20Murphy%2C%20G.%2C%20Gambus%2C%20A.%2C%20Petermann%2C%20E.%2C%20Stewart%2C%20G.%20S.%2C%20%26amp%3B%20Garc%26%23xED%3Ba%2C%20P.%20%282021%29.%20MYBL2%20and%20ATM%20suppress%20replication%20stress%20in%20pluripotent%20stem%20cells.%20%26lt%3Bi%26gt%3BEMBO%20Reports%26lt%3B%5C%2Fi%26gt%3B%2C%20%26lt%3Bi%26gt%3Bn%5C%2Fa%26lt%3B%5C%2Fi%26gt%3B%28n%5C%2Fa%29%2C%20e51120.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.15252%5C%2Fembr.202051120%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.15252%5C%2Fembr.202051120%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D6606345%26amp%3Bitem_key%3DPBBZHNPB%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22MYBL2%20and%20ATM%20suppress%20replication%20stress%20in%20pluripotent%20stem%20cells%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Blakemore%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nuria%22%2C%22lastName%22%3A%22Vilaplana-Lopera%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruba%22%2C%22lastName%22%3A%22Almaghrabi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elena%22%2C%22lastName%22%3A%22Gonzalez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Miriam%22%2C%22lastName%22%3A%22Moya%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carl%22%2C%22lastName%22%3A%22Ward%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22George%22%2C%22lastName%22%3A%22Murphy%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Agnieszka%22%2C%22lastName%22%3A%22Gambus%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eva%22%2C%22lastName%22%3A%22Petermann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Grant%20S%22%2C%22lastName%22%3A%22Stewart%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paloma%22%2C%22lastName%22%3A%22Garc%5Cu00eda%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20Replication%20stress%2C%20a%20major%20cause%20of%20genome%20instability%20in%20cycling%20cells%2C%20is%20mainly%20prevented%20by%20the%20ATR-dependent%20replication%20stress%20response%20pathway%20in%20somatic%20cells.%20However%2C%20the%20replication%20stress%20response%20pathway%20in%20embryonic%20stem%20cells%20%28ESCs%29%20may%20be%20different%20due%20to%20alterations%20in%20cell%20cycle%20phase%20length.%20The%20transcription%20factor%20MYBL2%2C%20which%20is%20implicated%20in%20cell%20cycle%20regulation%2C%20is%20expressed%20a%20hundred%20to%20a%20thousand-fold%20more%20in%20ESCs%20compared%20with%20somatic%20cells.%20Here%20we%20show%20that%20MYBL2%20activates%20ATM%20and%20suppresses%20replication%20stress%20in%20ESCs.%20Consequently%2C%20loss%20of%20MYBL2%20or%20inhibition%20of%20ATM%20or%20Mre11%20in%20ESCs%20results%20in%20replication%20fork%20slowing%2C%20increased%20fork%20stalling%20and%20elevated%20origin%20firing.%20Additionally%2C%20we%20demonstrate%20that%20inhibition%20of%20CDC7%20activity%20rescues%20replication%20stress%20induced%20by%20MYBL2%20loss%20and%20ATM%20inhibition%2C%20suggesting%20that%20uncontrolled%20new%20origin%20firing%20may%20underlie%20the%20replication%20stress%20phenotype%20resulting%20from%20loss%5C%2Finhibition%20of%20MYBL2%20and%20ATM.%20Overall%2C%20our%20study%20proposes%20that%20in%20addition%20to%20ATR%2C%20a%20MYBL2-MRN-ATM%20replication%20stress%20response%20pathway%20functions%20in%20ESCs%20to%20control%20DNA%20replication%20initiation%20and%20prevent%20genome%20instability.%22%2C%22date%22%3A%22March%2028%2C%202021%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.15252%5C%2Fembr.202051120%22%2C%22ISSN%22%3A%221469-221X%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2Ffull%5C%2F10.15252%5C%2Fembr.202051120%22%2C%22collections%22%3A%5B%5D%2C%22dateModified%22%3A%222021-03-31T18%3A48%3A17Z%22%7D%7D%5D%7D
Blakemore, D., Vilaplana-Lopera, N., Almaghrabi, R., Gonzalez, E., Moya, M., Ward, C., Murphy, G., Gambus, A., Petermann, E., Stewart, G. S., & García, P. (2021). MYBL2 and ATM suppress replication stress in pluripotent stem cells. EMBO Reports, n/a(n/a), e51120. https://doi.org/10.15252/embr.202051120 Cite

Cancer Stem Cell News
Cell Therapy News
Dermal Cell News
Endothelial Cell News
ESC & iPSC News
Extracellular Matrix News
Hematopoiesis News
Hepatic Cell News
Human Immunology News
Immune Regulation News
Intestinal Cell News
Mammary Cell News
Mesenchymal Cell News
Muscle Cell News
Neural Cell News
Organoid News
Pancreatic Cell News
Prostate Cell News
Pulmonary Cell News