Journal article

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

W Shi, T Vu, D Boucher, A Biernacka, J Nde, RK Pandita, J Straube, GM Boyle, F Al-Ejeh, P Nag, J Jeffery, JL Harris, AL Bain, M Grzelak, M Skrzypczak, A Mitra, N Dojer, N Crosetto, N Cloonan, OJ Becherel Show all

Blood | AMER SOC HEMATOLOGY | Published : 2017

Abstract

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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University of Melbourne Researchers

Grants

Awarded by National Institutes of Health


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.