SMC1B is present in mammalian somatic cells and interacts with mitotic cohesin proteins

Abstract

Cohesin is an evolutionarily conserved protein complex that plays a role in many biological processes: it ensures faithful chromosome segregation, regulates gene expression and preserves genome stability. In mammalian cells, the mitotic cohesin complex consists of two structural maintenance of chromosome proteins, SMC1A and SMC3, the kleisin protein RAD21 and a fourth subunit either STAG1 or STAG2. Meiotic paralogs in mammals were reported for SMC1A, RAD21 and STAG1/STAG2 and are called SMC1B, REC8 and STAG3 respectively. It is believed that SMC1B is only a meiotic-specific cohesin member, required for sister chromatid pairing and for preventing telomere shortening. Here we show that SMC1B is also expressed in somatic mammalian cells and is a member of a mitotic cohesin complex. In addition, SMC1B safeguards genome stability following irradiation whereas its ablation has no effect on chromosome segregation. Finally, unexpectedly SMC1B depletion impairs gene transcription, particularly at genes mapping to clusters such as HOX and PCDHB. Genome-wide analyses show that cluster genes changing in expression are enriched for cohesin-SMC1B binding.

Prdm9 and Meiotic Cohesin Proteins Cooperatively Promote DNA Double-Strand Break Formation in Mammalian Spermatocytes

“…The cohesin complexes are ring-shaped structures comprised of two structural maintenance-of-chromosome proteins (SMC1A or B and SMC3), a kleisin subunit (RAD21, RAD21L, or REC8), and a stromalin subunit (STAG1, 2, or 3) [3]. Of these components, STAG3, REC8, and RAD21L are expressed specifically during meiosis, presumably with unique meiotic function(s) [2][3][4][5][6][7][8][9][10][11]. Deletion or mutation of cohesin proteins affects axis length, SC formation, DNA double-strand break (DSB) repair, and chromatin organization during meiotic prophase in meiocytes [1,3,4,6,7,[11][12][13][14][15].…”

Cohesin Mutations in Myeloid Malignancies

“…These subunits form a heterotrimeric ring that encircles DNA and functions to maintain sister chromatid cohesion, facilitate DNA looping, and stabilize sites of double stranded DNA breaks [22,39,46,65]. Paralogs of SMC1A and STAG1 or STAG2, SMC1B and STAG3 respectively, were originally identified as being essential for meiotic cell division; however, recently these have also been identified in non-canonical cohesin complexes in somatic cells undergoing mitotic cell division [66,67]. Accessory subunits such as WAPAL, NIPBL, PDS5, CDC5A (sororin), ESCO1, and ESCO2 are required for different aspects of cohesin function [23].…”

Structural Maintenance of Chromosomes protein 1: Role in Genome Stability and Tumorigenesis

“…SMC1B is currently thought as a meiotic specific subunit of cohesin complex, called SMC1B, REC8 or STAG3 respectively 33 , which plays a key role in sister chromatid pairing and preventing telomere shortening 34 - 36 . Recent studies showed that SMC1B is also expressed in somatic mammalian cells as a member of a mitotic cohesin complex preserving genome stability in response to irradiation 37 .…”