Ssb1 and Ssb2 have essential and overlapping functions in adult stem cell homeostasis - granulocyte-macrophage progenitor data.

The single-stranded DNA binding proteins SSB1 and SSB2 are crucial regulators of the DNA damage response, however the overlapping functions of these related proteins is incompletely understood. We generated mice where both Ssb1 and Ssb2 were constitutively or conditionally deleted. Constitutive Ssb1/Ssb2 double knockout (DKO) caused early embryonic lethality, while conditional Ssb1/Ssb2 double knockout (cDKO) in adult mice resulted in acute lethality due to bone marrow failure and intestinal atrophy featured by stem and progenitor cell depletion. cDKO cells exhibited increased replication stress, R-loop accumulation, genome wide double strand breaks and cytosolic single-stranded DNA. Transcriptional profiling of cDKO cells revealed activation of p53 DNA damage and interferon responses. Hematopoietic stem and progenitor cells in cDKO mice showed enforced cell cycling, with subsequent apoptotic cell death. Collectively, these results demonstrate that Ssb1 and Ssb2 have compensatory functions in maintaining genomic stability and are collectively necessary for adult stem cell homeostasis.

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