title: Single strand DNA binding proteins 1 and 2 protect newly replicated telomeres.
abstract: Human single-strand (ss) DNA binding proteins 1 and 2 (hSSB1 and 2) are components of the hSSB1/2-INTS3-C9orf80 heterotrimeric protein complex shown to participate in DNA damage response and maintenance of genome stability. However, their roles at telomeres remain unknown. Here, we generated murine SSB1 conditional knockout mice and cells and found that mSSB1 plays a critical role in telomere end protection. Both mSSB1 and mSSB2 localize to a subset of telomeres and are required to repair TRF2-deficient telomeres. Deletion of mSSB1 resulted in increased chromatid-type fusions involving both leading- and lagging-strand telomeric DNA, suggesting that it is required for the protection of G-overhangs. mSSB1's interaction with INTS3 is required for its localization to damaged DNA. mSSB1 interacts with Pot1a, but not Pot1b, and its association with telomeric ssDNA requires Pot1a. mSSB1(Δ/Δ) mice die at birth with developmental abnormalities, while mice with the hypomorphic mSSB1(F/F) allele are born alive and display increased sensitivity to ionizing radiation (IR). Our results suggest that mSSB1 is required to maintain genome stability, and document a previously unrecognized role for mSSB1/2 in the protection of newly replicated leading- and lagging-strand telomeres.
authors: Department of Laboratory Medicine and Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Peili
authors: P
authors: Gu
authors: Wei
authors: W
authors: Deng
authors: Ming
authors: M
authors: Lei
authors: Sandy
authors: S
authors: Chang
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D002842:Chromatids / Q000378:metabolism; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D000089804:Shelterin Complex; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C507326:POT1 protein, mouse; D034741:RNA, Small Interfering; C577279:SSBP1 protein, mouse; D000089804:Shelterin Complex; C504092:Ssbp2 protein, mouse; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2