Single strand DNA binding proteins 1 and 2 protect newly replicated telomeres

Area of Science:

• Molecular Biology
• Genetics
• Cell Biology

Background:

• Human single-strand DNA binding proteins 1 and 2 (hSSB1/2) are part of a complex involved in DNA damage response and genome stability.
• The specific roles of hSSB1/2 at telomeres have not been previously elucidated.

Purpose of the Study:

• To investigate the function of murine SSB1 (mSSB1) and mSSB2 in telomere maintenance and genome stability.
• To determine the molecular mechanisms underlying mSSB1's role at telomeres, including its interactions with other proteins and its requirement for telomere end protection.

Main Methods:

• Generation of murine SSB1 conditional knockout mice and cell lines.
• Analysis of telomere structure and function in mSSB1 deficient cells and mice.
• Investigation of protein-protein interactions between mSSB1, INTS3, and Pot1a/b.

Main Results:

• mSSB1 and mSSB2 were found to localize to a subset of telomeres and are essential for repairing TRF2-deficient telomeres.
• Deletion of mSSB1 caused increased chromatid-type fusions at telomeres, indicating a role in protecting G-overhangs.
• mSSB1's interaction with INTS3 is necessary for its recruitment to damaged DNA, and its telomeric ssDNA association requires Pot1a.

Conclusions:

• mSSB1 plays a critical role in telomere end protection and maintaining genome stability.
• mSSB1/2 are involved in the protection of both leading- and lagging-strand telomeres during replication.
• mSSB1 deficiency leads to embryonic lethality or increased sensitivity to ionizing radiation, underscoring its importance in vivo.