Single-stranded DNA-binding proteins at healthy and diseased telomeres

The repetitive G-/C-rich nature of telomeres makes them potent obstacles to replicative DNA polymerases, eliciting a state of replication stress during genome duplication. Within replisomes and as part of the shelterin complex, numerous single-stranded DNA (ssDNA)-binding proteins (SSBPs) help maintain telomere homeostasis by protecting specific telomeric structures and managing replication stress. Underlining their critical roles, mutations in key ssDNA binders influence telomere length, cause telomeropathies, and/or act as drivers of cancer development. Here, we review recent findings on the roles of SSBPs and their coordination during telomere replication and elongation. We also present recent advances on ssDNA-binding factors and their regulators in alternative lengthening of telomeres (ALTs), highlighting how these findings may provide viable therapeutic targets in ALT cancers.