Journal article

Ssb1 and Ssb2 cooperate to regulate mouse hematopoietic stem and progenitor cells by resolving replicative stress

Wei Shi, Therese Vu, Didier Boucher, Anna Biernacka, Jules Nde, Raj K Pandita, Jasmin Straube, Glen M Boyle, Fares Al-Ejeh, Purba Nag, Jessie Jeffery, Janelle L Harris, Amanda L Bain, Marta Grzelak, Magdalena Skrzypczak, Abhishek Mitra, Norbert Dojer, Nicola Crosetto, Nicole Cloonan, Olivier J Becherel Show all

BLOOD | AMER SOC HEMATOLOGY | Published : 2017


Hematopoietic stem and progenitor cells (HSPCs) are vulnerable to endogenous damage and defects in DNA repair can limit their function. The 2 single-stranded DNA (ssDNA) binding proteins SSB1 and SSB2 are crucial regulators of the DNA damage response; however, their overlapping roles during normal physiology are incompletely understood. We generated mice in which both Ssb1 and Ssb2 were constitutively or conditionally deleted. Constitutive Ssb1/Ssb2 double knockout (DKO) caused early embryonic lethality, whereas conditional Ssb1/Ssb2 double knockout (cDKO) in adult mice resulted in acute lethality due to bone marrow failure and intestinal atrophy featuring stem and progenitor cell depletion,..

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Awarded by National Health and Medical Research Council (NHMRC)

Awarded by National Institutes of Health from the National Cancer Institute

Awarded by National Institute of General Medical Sciences

Awarded by Polish National Science Centre



Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) (NHMRC1085367) (K.K.K. and S.W.L.); the National Institutes of Health (grants CA129537 and CA154320 [T.K.P.] from the National Cancer Institute and grants GM109768 [T.K.P.] and GM112131 [M.R., J.N., and N.D.] from the National Institute of General Medical Sciences); the Polish National Science Centre (grants 2011/02/A/NZ2/00014, 2014/15/B/NZ1/03357, and 2015/17/D/NZ2/03711) (K.G., M.S., A.B., and M.G.); the Foundation for Polish Science (grant TEAM) (K.G., M.S., and A.B.); and an NHMRC Senior Principal Research Fellowship (K.K.K.). S.W.L. is an NHMRC Career Development Fellow, and T.V. is a Leukaemia Foundation PhD Scholar.